Trisomy 14 Mosaicism Including Concomitant Uniparental Disomy: Population Frequency, Cytogenetic Profile, Sex Ratio, Maternal Age and Obstetric History
Academy of Molecular Medicine, St. Petersburg, Russian Federation
ResearchDx Inc., Irvine, CA, USA
Academic Editor: Jaclyn Murry
Special Issue: Mosaicism and Chimerism
Received: May 02, 2022 | Accepted: August 11, 2022 | Published: September 05, 2022
OBM Genetics 2022, Volume 6, Issue 3, doi:10.21926/obm.genet.2203162
Recommended citation: Kovaleva NV, Cotter PD. Trisomy 14 Mosaicism Including Concomitant Uniparental Disomy: Population Frequency, Cytogenetic Profile, Sex Ratio, Maternal Age, and Obstetric History. OBM Genetics 2022;6(3):30; doi:10.21926/obm.genet.2203162.
© 2022 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.
Trisomy for chromosome 14 is lethal; individuals only with the mosaic form can survive. The first patient with this chromosomal abnormality was described in 1970 . Mosaicism for trisomy of chromosome 14 (mosT14) is not characterized epidemiologically due to its rarity. Therefore, we conducted a systematic review of published cases to address the epidemiological aspects of this abnormality. The data were retrieved from various resources, including PubMed, Research Gate, and the ChromosOmics UPD Database . We also conducted a comparative analysis of the parameters in spontaneous abortions and carriers of uniparental disomy (UPD) of chromosome 14 caused by non-mosaic rearrangements.
For a comprehensive analysis of the cytogenetic profile and other parameters under consideration, describing the mechanism of mosT14 formation is important. Mosaicism for regular trisomy might arise due to meiotic nondisjunction followed by mitotic loss of the trisomic chromosome, also known as “trisomy correction” or “trisomy rescue”. This mechanism leads to the restoration of biparental inheritance (BD, biparental disomy) in two-thirds of the cases and uniparental disomy (UPD) in one-third of the cases. This may lead to the expression of clinical features of both mosT14 and UPD(14). Few cases of mixed mosaic trisomy in the same individual have been described, where a cell line with BD coexists with a cell line with UPD; the first case was reported by McCaskill et al. in 1995 . Complete trisomy rescue leads to a non-mosaic euploid condition, with or without biparentally derived homologs or (rarely) with mosaicism for UPD, as mentioned above. In a few cases, mosT14 results from postzygotic mitotic nondisjunction.
Mosaicism for trisomy 14 caused by unbalanced non-homologous Robertsonian translocation, either inherited (in most cases) or de novo, typically arises due to rescue as well. The main mechanism of mosaicism associated with homologous translocation/isochromosome is mitotic, caused by the formation of an isochromosome and trisomy rescue. Euploid zygotes with non-mosaic homologous translocations/isochromosomes may also be formed by “gametic complementation”, which is the fusion of two abnormal gametes, nullisomic for a specific chromosome and gamete with translocation disomy occurring in the same chromosome . Additionally, monosomy rescue might occur in the first zygotic cleavage (perizygotic error) . As first observed by Robinson et al. , all homologous rearrangements with UPD are isochromosomes.
2. Population Frequency
The frequency of liveborn carriers of mosT14 in the population showing clinical manifestation cannot be accurately calculated because they are extremely rare. The only data available for analysis are surveys on the spontaneous loss of pregnancy. From published studies, we selected 61 reports where the cytogenetic profile was clearly described (data available on request). Overall, 194 cases of regular T14 and two cases of mosaic T14 among 21,082 tested spontaneous abortuses (0.9% and 0.09‰, respectively) were identified. The two cases of mosaic T14 were identified by conventional cytogenetic testing; one was identified among 259 products of conception (POC) after the first trimester , while the other one was identified among 543 POC after 7–34 weeks of gestation . The rarity of mosaic cases might be due to underdiagnosis.
However, data from a cytogenetic survey on 10,730 recurrent pregnancy losses (not included in the above-mentioned list of 61 reports), where non-mosaic T14 was detected in about 6% of full aneuploidies, supported the conclusion regarding the low frequency of mosaic T14. The study did not report any case of mosaicism for T14, although mosaic trisomies of chromosomes 16, 13, 2, and 22 were identified in 0.35%, 0.35%, 0.28%, and 0.21% of aneuploid POC . This observation was intriguing since mosaics are more viable than full trisomy carriers. Alternatively, it might be possible that almost all mosaic T14 infants survive to term.
3. Cytogenetic Profile of Mosaicism
Among 76 carriers of mosaicism for trisomy 14, 50 carriers showed mosaicism for regular MT14 (10 prenatal and 40 postnatal), 21 carriers showed mosaicism for unbalanced homologous translocation/isochromosome 14 (three prenatal, one stillborn, and 17 postnatal), and five carriers showed mosaicism for unbalanced non-homologous Robertsonian translocation involving chromosome 14 (one prenatal, one miscarriage, and three postnatal). The cytogenetic profile of trisomy 14 was not significantly different between prenatal (n = 16) and postnatal (n = 60) diagnoses; 63% were carriers of regular trisomy, 25% were carriers of homologous unbalanced translocation/isochromosome, and 12% were carriers of unbalanced non-homologous translocation among prenatally detected individuals, while 67%, 28%, and 5% were carriers among postnatally diagnosed individuals, respectively (Table 1, Table 2 and Table 3 [10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77]).
Our finding that mosaicism for regular T14 dominates mosaicism due to unbalanced translocation/isochromosome was similar to the findings of other studies, which reported that full trisomies predominate visible chromosomal abnormalities. In contrast, homologous translocations predominate nonhomologous translocations. This observation is interesting since nonhomologous translocations are very common chromosome rearrangements found both in consecutive newborns and in prenatal diagnosis, whereas homologous translocations are extremely rare. Among 93,716 tested newborns, 96 carriers of non-homologous translocation were diagnosed, and no carriers of homologous translocations were identified. Among 221 prenatally detected carriers of Robertsonian translocation, only two females were reported as carriers of a homologous translocation: 45, XX, t(13;13) and 45, XX, t(15;15) (see review ).
The proportion of homologous translocations/isochromosomes in the studied mosaic group (21 of 26) was significantly different than that in the carriers of non-mosaic UPD(14) associated with balanced translocations (Table 4 [6,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113]), with the prevalence of non-homologous translocations (29 of 50; p = 0.0029) (Chi-squared test; Yates-corrected). Overall, these observations supported a preferential mitotic mechanism of homologous translocation/isochromosome formation . The relatively higher proportion of homologous translocations in non-mosaic UPD(14) carriers needs further investigation.
In the group of mosaic unbalanced homologous translocation/isochromosome 14, there were a number of carriers with a cell line containing a ring chromosome (3 of 19). Several studies have reported the association of ring chromosomes with homologous translocations, including chromosomes 13 , 15 , 21 , and 18 . Stetten et al. suggested that a homologous translocation was necessary for the formation of ring chromosomes .
The parental origin of the diploid cell line was examined in 39 individuals; among them, 17 were diagnosed with maternal UPD(14), two had paternal UPD(14), and the remaining 20 demonstrated biparental inheritance. Theoretically, only one-third of the cases with mosaics for regular T14 might be expected to be UPD carriers. However, the observed ratio of UPD(14) to BD of 15:12 differed from the expected ratio, probably because of publication bias (i.e., the tendency to publish more “interesting” cases of uniparental disomy). The ratio of paternal UPD to maternal UPD (2 of 15) of 2:13 might occur because of more frequent chromosome nondisjunction during oogenesis.
4. Sex Ratio (Male-to-Female Ratio)
Most mosT14 patients were females in all studied groups irrespective of whether the trisomic line was regular or caused due to an unbalanced rearrangement and independent of the parental origin of the euploid line. Data reviewed from 26 published reports (Table 5 [7,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144]) on 48 males and 66 females showed that male cases were not predominant among abortuses with T14 (sex ratio of 0.70, in contrast to trisomies 13 and 21 with a sex ratio of 1.1 and 1.4, respectively). Therefore, a female-biased sex ratio in the studied groups cannot be explained by high intrauterine male mortality.
A comparison of the two datasets supported the hypothesis of very early mortality of T14 male carriers. In a large series (n = 534) of spontaneous miscarriages of 7–34 weeks of gestation, one male and 14 female carriers of mosaicism for autosomal trisomy (3%) were identified by conventional cytogenetics; among them, one was a female mosaic for T14 (46, XX/47, XX, +14) . In a smaller sample (n = 60) of spontaneous abortions of 5–12 weeks of gestation, the results of the interphase FISH analysis revealed nine males and six females with mosaicism for autosomal trisomy (25%), one of them being a male mosaic for T14 .
If males are less tolerant to the presence of T14 cells, they are expected to have a lower frequency of trisomic cells than females. Since many patients, for various reasons, were not examined using modern techniques, we analyzed a proportion of trisomic cells from the blood cultures of 11 male patients and 46 female patients. Male patients had a lower proportion of trisomic cells than female patients, with average frequencies of 16.3% (0%-70%) and 20.1% (0%-93%). Comparing the clinical manifestation of the mosaic T14 in male and female carriers was difficult because of few reported cases.
The observed four-fold female predominance among mosT14 (19 males/57 females) cannot be explained entirely by a male intolerance to the presence of T14 cells, since this pattern is also observed in the carriers of UPD(14) without mosaicism for T14 (16 males/34 females), particularly to paternal UPD(14) (3 males/18 females). We speculated that the observed female predominance might be explained by female-specific instabilities of pericentromeric regions , female-specific trisomy correction , and male-specific selection against abnormal cells .
5. Maternal Factors
5.1 Maternal Age
Data on maternal age was available for 38 postnatally diagnosed patients; their average age was 28.7 years, and 18% of the mothers were 35 years and above. The origin of the diploid cell line was determined in a subset of these patients; 11 were of biparental origin, and five had maternal uniparental disomy. The average maternal age in the BD group was 29.8 years (18–43 years), and 18% of the mothers were above 35 years. The average maternal age in the UPD group was 35.4 years (32–40 years), and 80% of the mothers were above 35 years. The difference between these groups was statistically significant (p < 0.05; Mann-Whitney U test).
Although the association of UPD with advanced maternal age is well-established , Mitter et al.  suggested that maternal age does not increase the risk of maternal UPD(14), unlike maternal UPD(15). Therefore, our finding is even more intriguing, especially considering the common mechanism of the formation of BP and UPD. As mentioned previously, the sample size was small and more studies on mosT14 need to be published.
5.2 Maternal Reproductive History
Unfortunately, information on maternal reproductive history is limited. After excluding primigravida women and carriers of non-homologous translocation, data on 44 mothers were available. Among them, even after we disregarded the low quality of the anamnesis description (for example, healthy child, first-born child, G2PO, etc.), there were 11 (or 25%) families with complicated reproductive history (including previous spontaneous abortion(s), infertility, etc.). The estimated rate of reproductive disorders in the population was approximately 12.5% for families .
Chromosomal mosaicism might not be transmitted. However, genetic predisposition to mitotic nondisjunction might occur; mosaicism for T21 in successive generations was reported in at least 12 of 80 families of gonadal mosaicism (see review ). Gonadal mosaicism may cause reproductive disorders and abnormalities in offspring. Further studies on such cases are required for accurately determining the complicated reproductive history as a risk factor for T14 mosaicism.
This was the first systematic review of published cases of mosaic trisomy 14 to address epidemiological aspects of this abnormality. The analysis of the data provided an initial epidemiological evaluation of this rare disorder. Conducting a more detailed analysis is challenging due to the under-reporting of cases. Even when cases are reported, limited data on parameters such as genetic testing, the karyotype and age of the patient, the age of the parents when the patient was born, and parental reproductive history have been reported, despite being readily available at the first examination of the patient. Developing consensus protocols for reporting cases to registries or public databases can benefit future studies.
Both authors equally contributed to this paper.
The authors have declared that no competing interests exist.
- Murken JD, Bauchinger M, Palitzsch D, Pfeifer H, Suschke J, Haendle H. Trisomy D2 in a 2 and one-half year old girl (47,XX,14+). Humangenetik. 1970; 10: 254-268. [CrossRef]
- Liehr T. Cases with uniparental disomy [Internet]. Available from: http://cs-tl.de/DB/CA/UPD/0-Start.html.
- McKaskill C, Subramanian S, Hughes M, Shaffer LG. Single-cell analysis of mosaic trisomy 21: Origin and mechanisms of mosaicism. Am J Hum Genet. 1995; 57: 254.
- Berend SA, Feldman GL, McCaskill C, Czarnecki P, Van Dyke DL, Shaffer LG. Investigation of two cases of paternal disomy 13 suggests timing of isochromosome formation and mechanisms leading to uniparental disomy. Am J Med Genet. 1999; 82: 275-281. [CrossRef]
- Gardner RJ, Parslow MI, Veale AM. The formation of the abnormal chromosome in balanced homologous Robertsonian translocation carriers. Humangenetik. 1974; 21: 270-282. [CrossRef]
- Robinson WP, Bernasconi F, Basaran S, Yüksel-Apak M, Neri G, Serville F, et al. A somatic origin of homologous Robertsonian translocations and isochromosomes. Am J Hum Genet. 1994; 54: 290-302.
- Ljunger E, Cnattingius S, Lundin C, Annerén G. Chromosomal anomalies in first-trimester miscarriages. Acta Obstet Gynecol Scand. 2005; 84: 1103-1107. [CrossRef]
- Jenderny J. Chromosome aberrations in a large series of spontaneous miscarriages in the German population and review of the literature. Mol Cytogenet. 2014; 7: 38. [CrossRef]
- Yatsenko SA, Quesada-Candela C, Saller DN, Beck S, Jaffe R, Kostadinov S, et al. Cytogenetic signatures of recurrent pregnancy losses. Prenat Diagn. 2021; 41: 70-78. [CrossRef]
- Burns J, Arsham M, Adomaitis L, Christian J, Ligi R, Kazimi S. FISH (Fluorescent in Situ Hybridization) confirming a mosaic trisomy 14 in a newborn. Am J Hum Genet. 2001; 69: 332.
- Keitges EA, Skogerboe KJ, Luthard FW. Mosaic trisomy 14 diagnosed at amniocentesis, confirmed in CVS cultures, but absent in fetal skin cultures. Cytogenet Cell Genet. 1993; 63: 251.
- Phelan DG, Flowers N, Giouzeppos O, Lall P, Casey E, Houben L, et al. Genome-wide cell-free DNA based noninvasive prenatal testing identifies trisomy 14 mosaicism in association with uniparental disomy. Pathology. 2020; 52: S27. [CrossRef]
- Ralph A, Scott F, Tiernan C, Caubere M, Kollegger S, Junio J, et al. Maternal uniparental isodisomy for chromosome 14 detected prenatally. Prenat Diagn. 1999; 19: 681-684. [CrossRef]
- Sanlaville D, Aubry MC, Dumez Y, Nolen MC, Amiel J, Pinson MP, et al. Maternal uniparental heterodisomy of chromosome 14: Chromosomal mechanism and clinical follow up. J Med Genet. 2000; 37: 525-528. [CrossRef]
- Sirchia SM, De Andreis C, Pariani S, Grimoldi MG, Molinari A, Buscaglia M, et al. Chromosome 14 maternal uniparental disomy in the euploid cell line of a fetus with mosaic 46,XX/47,XX,+14 karyotype. Hum Genet. 1994; 94: 355-358. [CrossRef]
- Suzumori N, Kagami M, Kumagai K, Goto S, Matsubara K, Sano S, et al. Clinical and molecular findings in a patient with 46,XX/47,XX,+14 mosaicism caused by postzygotic duplication of a paternally derived chromosome 14. Am J Med Genet. 2015; 167: 2474-2477. [CrossRef]
- Towner DR1, Shaffer LG, Yang SP, Walgenbach DD. Confined placental mosaicism for trisomy 14 and maternal uniparental disomy in association with elevated second trimester maternal serum human chorionic gonadotrophin and third trimester fetal growth restriction. Prenat Diagn. 2001; 21: 395-398. [CrossRef]
- Wegner RD, Hohle R, Karkut G, Sperling K. Trisomy 14 mosaicism leading to cytogenetic discrepancies in chorionic villi sampled at different times. Prenat Diagn. 1988; 8: 239-243. [CrossRef]
- Witters I, Moerman P, Fryns JP. First-trimester scan in trisomy 14 mosaicism. Prenat Diagn. 2004; 24: 573-574. [CrossRef]
- Balbeur S, Grisart B, Parmentier B, Sartenaer D, Leonard PE, Ullmann U, et al. Trisomy rescue mechanism: The case of concomitant mosaic trisomy 14 and maternal uniparental disomy 14 in a 15-year-old girl. Clin Case Rep. 2016; 4: 265-271. [CrossRef]
- Becerra-Solano LE, Arnaud-Lopez L, Diaz-Rodriguez M, Mantilla-Capacho JM, Nastasi-Catanese JA, Ortiz-Aranda M, et al. First case reported of Turner syndrome and trisomy 14 chromosomal mosaicism in a patient. Clin Dysmorphol. 2008; 17: 27-30. [CrossRef]
- Cheung SW, Shaw CA, Scott DA, Patel A, Sahoo T, Bacino CA, et al. Microarray-based CGH detects chromosomal mosaicism not revealed by conventional cytogenetics. Am J Med Genet. 2007; 143: 1679-1686. [CrossRef]
- Choi JH, Choi YJ, Kim SY. Congenital ocular anomaly in an infant with trisomy 14 mosaicism. Korean J Ophthalmol. 2012; 26: 316-318. [CrossRef]
- Conlin LK, Thiel BD, Bonnemann CG, Medne L, Ernst LM, Zackai EH, et al. Mechanisms of mosaicism, chimerism and uniparental disomy identified by single nucleotide polymorphism array analysis. Hum Mol Genet. 2010; 19: 1263-1275. [CrossRef]
- Cox H, Bullman H, Temple IK. Maternal UPD(14) in the patient with a normal karyotype: Clinical report and a systematic search for cases in samples sent for testing for Prader-Willi syndrome. Am J Med Genet A. 2004; 127: 21-25. [CrossRef]
- Dallapiccola B, Ferranti G, Giannotti A, Novelli G, Pasquini L, Porfirio B. A live infant with trisomy 14 mosaicism and nuclear abnormalities of the neutrophils. J Med Genet. 1984; 21: 467-470. [CrossRef]
- Eventov-Friedman S, Frumkin A, Bar-Oz B, Raas-Rothschild A. Mosaic trisomy 14 in a newborn with multiple malformations: When chromosomal microarray is a clue to diagnosis. Isr Med Assoc J. 2015; 17: 459-460.
- Fujimoto A, Allanson J, Crowe CA, Lipson MH, Johnson VP. Natural history of mosaic trisomy 14 syndrome. Am J Med Genet. 1992; 44: 189-196. [CrossRef]
- He M, Pepperell JR, Gundogan F, De Paepe ME, Maggio L, Lu S, et al. Monochorionic twins discordant for mosaic trisomy 14. Am J Med Genet A. 2014; 164: 1227-1233. [CrossRef]
- Hur YJ, Hwang T. Complete trisomy 14 mosaicism: First live-born case in Korea. Korean J Pediatr. 2012; 55: 393-396. [CrossRef]
- Iglesias A, McCurdy LD, Glass IA, Cotter PD, Illueca M, Perenyi A, et al. Mosaic trisomy 14 with hepatic involvement. Ann Genet. 1997; 40: 104-108.
- Jenkins L, Levy H, Chen E, Li X, Jones J, Schoof J, et al. Detection of mosaicism and UPD14 in a baby with Prader-Willi like features. Am J Hum Genet. 2009; 85: 421.
- Johnson VP, Aceto T Jr, Likness C. Trisomy 14 mosaicism: Case report an review. Am J Med Genet. 1979; 3: 331-339. [CrossRef]
- Kaplan LC, Wayne A, Crowell S, Latt SA. Trisomy 14 mosaicism in a liveborn male: Clinical report and review of the literature. Am J Med Genet. 1986; 23: 925-930. [CrossRef]
- Kryukova NM, Katran LL, Zavorotnaya NM, Golihina TA, Matulevich SA. Chromosome 14 trisomy in a 2 years old girl. Med Genet. 2005; 4: 213.
- Lindgren V, Cobian K, Bhat G. Temple syndrome resulting from uniparental disomy is undiagnosed by a methylation assay due to low-level mosaicism for trisomy 14. Am J Med Genet A. 2021; 185: 1538-1543. [CrossRef]
- Lipson MH. Trisomy 14 mosaicism syndrome. Am J Med Genet. 1987; 26: 541-544. [CrossRef]
- Fran Lynch M, Fernandes CJ, Shaffer LG, Potocki L. Trisomy 14 mosaicism: A case report and review of the literature. J Perinatol. 2004; 24: 121-123. [CrossRef]
- Martin AO, Ford MM, Khalil NT, Turk KB, Macintyre MN. 46,XX/47XX,+14 mosaicism in a liveborn infant. J Med Genet. 1977; 14: 214-233. [CrossRef]
- Massara LS, Delea M, Espeche L, Bruque CD, Oliveri J, Brun P, et al. Double autosomal/gonosomal mosaic trisomy 47,XXX/47,XX,+14 in a newborn with multiple congenital anomalies. Cytogenet Genome Res. 2019; 159: 137-142. [CrossRef]
- McGaughran J, Stevens R, Blond A, Perry C. Nasal encephalocele in a child with mosaic trisomy 14. Clin Dysmorphol. 2009; 18: 164-165. [CrossRef]
- Merritt TA, Natarajan G. Trisomy 14 mosaicism: A case without evidence of neurodevelopmental delay and a review of the literature. Am J Perinatl. 2007; 24: 563-566. [CrossRef]
- Mucha-Le Ny BE, Kalish JM, Spinner NB, Zackai E, Conlin LK. Paternal UPD14 diagnosed by whole genome array: Clinical and radiological features. Am J Hum Genet. 2010; 87: 252.
- Petersen MB, Vejerslev LO, Beck B. Trisomy 14 mosaicism in a 2 year old girl. J Med Genet. 1986; 23: 86-88. [CrossRef]
- Fagerberg CR, Eriksen FB, Thormann J, Østergaard JR. Trisomy 14 mosaicism: Clinical and cytogenetic findings in an adult. Clin Dysmorphol. 2012; 21: 45-47. [CrossRef]
- Rethoré MO, Couturier J, Carpentier S, Ferrand J, Lejeune J. Mosaic 14 trisomy in a female child with multiple abnormalities. Ann Genet. 1975; 18: 71-74.
- Rodrigues MA, Morgade LF, Dias LF, Moreira RV, Maia PD, Sales AF, et al. Low-level trisomy 14 mosaicism in a male newborn with ectrodactyly. Genet Mol Res. 2016; 15: gmr15049275. [CrossRef]
- Salas-Labadía C, Lieberman E, Cruz-Alcívar R, Navarrete-Meneses P, Gómez S, Cantú-Reyna C, et al. Partial and complete trisomy 14 mosaicism: Clinical follow-up, cytogenetic and molecular analysis. Mol Cytogenet. 2014; 7: 65. [CrossRef]
- Sepulveda W, Monckeberg MJ, Be C. Twin pregnancy discordant for trisomy 14 mosaicism: Prenatal sonographic findings. Prenat Diagn. 1998; 18: 481-484. [CrossRef]
- Shinawi M, Shao L, Jeng LJ, Shaw CA, Patel A, Bacino C, et al. Low-level mosaicism of trisomy 14: Phenotypic and molecular characterization. Am J Med Genet A. 2008; 146: 1395-1405. [CrossRef]
- Stalman SE, Kamp GA, Hendriks YM, Hennekam RC, Rotteveel J. Positive effect of growth hormone treatment in maternal uniparental disomy chromosome 14. Clin Endocrinol. 2015; 83: 671-676. [CrossRef]
- Ushijima K, Yatsuga S, Matsumoto T, Nakamura A, Fukami M, Kagami M. A severely short-statured girl with 47,XX,+14/46,XX, UPD(14) mat, mosaicism. J Hum Genet. 2018; 63: 377-381. [CrossRef]
- Vachvanichsanong P, Jinorose U, Sangnuachua P. Trisomy 14 mosaicism in a 5-year-old boy. Am J Med Genet. 1991; 40: 80-83. [CrossRef]
- Yakoreva M, Kahre T, Pajusalu S, Ilisson P, Žilina O, Tillmann V, et al. A new case of a rare combination of temple syndrome and mosaic trisomy 14 and a literature review. Mol Syndromol. 2018; 9: 182-189. [CrossRef]
- Zhang S, Qin H, Wang J, Yang L, Luo S, Fu C, et al. Maternal uniparental disomy 14 and mosaic trisomy 14 in a Chinese boy with moderate to severe intellectual disability. Mol Cytogenet. 2016; 9: 66. [CrossRef]
- Chen CP, Wang KG, Ko TM, Chern SR, Su JW, Town DD, et al. Mosaic trisomy 14 at amniocentesis: Prenatal diagnosis and literature review. Taiwan J Obstet Gynecol. 2013; 52: 446-449. [CrossRef]
- Hsu LY, Yu MT, Richkind KE, Van Dyke DL, Crandall BF, Saxe DF, et al. Incidence and significance of chromosome mosaicism involving an autosomal structural abnormality diagnosed prenatally through amniocentesis: A collaborative study. Prenat Diagn. 1996; 16: 1-28. [CrossRef]
- Lambert I, Kemp J, Jackson J, Joyce H, Mann S, Kan A, et al. Prenatal diagnosis and post-mortem study of a fetus with mosaic trisomy 14 due to a dic(14)(p11). Prenat Diagn. 1994; 14: 507-510. [CrossRef]
- Wang JC, Li CF, Shaw DR. Prenatally diagnosed mosaic trisomy 14q with omphalocele. Prenat Diagn. 2007; 27: 1260-1261. [CrossRef]
- Cantú ES, Thomas IT, Frias JL. Unusual cytogenetic mosaicism involving chromosome 14 abnormalities in a child with an MR/MCA syndrome and abnormal pigmentation. Clin Genet. 1989; 36: 189-195. [CrossRef]
- Cheung SW, Kolacki PL, Watson MS, Crane JP. Prenatal diagnosis, fetal pathology, and cytogenetic analysis of mosaic trisomy 14. Prenat Diagn. 1988; 8: 677-682. [CrossRef]
- Jenkins MB, Kriel R, Boyd L. Trisomy 14 mosaicism in a translocation 14q15q carrier: Probable dissociation and isochromosome formation. J Med Genet. 1981; 18: 68-71. [CrossRef]
- Katahira M, Kayashima T, Kishino T, Niikawa N. Maternal uniparental disomy for chromosome 14 with diabetes mellitus. Intern Med. 2002; 41: 717-721. [CrossRef]
- Kolotiy AD, Yablonskaya MI, Yurov YB, Kurinnaya OS, Kravets VS, Yourov IY, et al. Combination of mosaic trisomy 14 chromosome and type 1 neurofibromatosis in a child: Challenges of genetic diagnostics. 2020. Doi: 10.17513/spno.29865. [CrossRef]
- Ozawa N, Xu ZD, Soh K, Takabayashi T, Sato S, Yajima A, et al. A case of mosaic trisomy 14 due to an isochromosome, i(14q). Jpn J Hum Genet. 1984; 29: 69-76. [CrossRef]
- Pangalos C, Velissariou V, Ghica M, Liacacos D. Ring-14 and trisomy 14q in the same child. Ann Genet. 1984; 27: 38-40.
- Smith KK, Boyle TA, Morgan DL, Parkin CA. Uniparental disomy: UK Collaborative Study. Am J Hum Genet. 2001; 69: 338.
- Thomas IT, Frias JL, Cantu ES, Lafer CZ, Flannery DB, Graham JG Jr. Association of pigmentary anomalies with chromosomal and genetic mosaicism and chimerism. Am J Hum Genet. 1989; 45: 193-205.
- Tunca Y, Wilroy RS, Kadandale JS, Martens PR, Gunther WM, Tharapel AT. Hypomelanosis of Ito and a 'mirror image' whole chromosome duplication resulting in trisomy 14 mosaicism. Ann Genet. 2000; 43: 39-43. [CrossRef]
- Turleau C, de Grouchy J, Cornu A, Turquet M, Millet G. Mosaic trisomy 14 due to an iso dicentric chromosome (author's transl). Ann Genet. 1980; 23: 238-240.
- Velissariou V, Sachinidi F, Christopoulou S, Florentin L, Liehr T, Efthymiadou A, et al. Low-level trisomy 14 mosaicism: A carrier of an isochromosome 14 and a supernumerary marker chromosome 14. Cytogenet Genome Res. 2020; 160: 664-670. [CrossRef]
- von Sneidern E, Lacassie Y. Is trisomy 14 mosaic a clinically recognizable syndrome? Case report and review. Am J Med Genet. 2008; 146: 1609-1613. [CrossRef]
- Taucher SC, Fuentes Soto AM, Millanao AP, de la Rosa Rebaza E. Estudio cromosómico en abortos espontáneos. Rev Chil Obstet Ginecol. 2014; 79: 40-46. [CrossRef]
- Wu WJ, Ma GC, Lee MH, Chen YC, Chen M. Normal prenatal ultrasound findings reflect outcome in case of trisomy 14 confined placental mosaicism developing after preimplantation genetic diagnosis. Ultrasound Obstet Gynecol. 2017; 50: 128-130. [CrossRef]
- Antonarakis SE, Blouin JL, Maher J, Avramopoulos D, Thomas G, Talbot CC Jr. Maternal uniparental disomy for human chromosome 14, due to loss of a chromosome 14 from somatic cells with t(13;14) trisomy 14. Am J Hum Genet. 1993; 52: 1145-1152.
- Barton DE, McQuaid S, Stallings R, Griffin E, Geraghty M. Further evidence for an emerging maternal uniparental disomy chromosome 14 syndrome: Analysis of a phenotypically abnormal de novo Robertsonian translocation t(13;14) carrier. Am J Hum Genet. 1996; 59: 698.
- Fujimoto A, Lin MS, Korula SR, Wilson MG. Trisomy 14 mosaicism with t(14;15)(q11;p11) in offspring of a balanced translocation carrier mother. Am J Med Genet. 1985; 22: 333-342. [CrossRef]
- Kovaleva NV. Examination of rates and spectrums of robertsonian translocations in general population and in patients with reproductive disorders. Russ J Genet. 2018; 54: 508-512. [CrossRef]
- Bertini V, Fogli A, Bruno R, Azzarà A, Michelucci A, Mattina T, et al. Maternal uniparental disomy 14 (Temple syndrome) as a result of a Robertsonian translocation. Mol Syndromol. 2017; 8: 131-138. [CrossRef]
- Harrison KJ, Allingham-Hawkins DJ, Hummel J, Meschino WS, Cox DW, Costa TM, et al. Risk of uniparental disomy in Robertsonian translocation carriers: Identification of UPD14 in a small cohort. Am J Hum Genet. 1998; 63: A11.
- Link L, McMillin K, Popovich B, Magenis RE. Maternal uniparental disomy for chromosome 14. Am J Hum Genet. 1996; 59: 687.
- Mitter D, Buiting K, von Eggeling F, Kuechler A, Liehr T, Mau-Holzmann UA, et al. Is there a higher incidence of maternal uniparental disomy 14 [UPD(14)mat]? Detection of 10 new patients by methylation-specific PCR. Am J Med Genet. 2006; 140: 2039-2049. [CrossRef]
- Rocha MG, Pinto-Basto J, Garcia E, Reis Lima M, Pinto M, Fortuna A. Maternal uniparental disomy of chromosome [mUPD(14)] in a boy with rob(13;14)mat. Eur J Hum Genet. 2006; 14: 139.
- Worley KA, Rundus VR, Lee EB, Hannig VL, Hedges LK, Tsuchiya K, et al. Maternal uniparental disomy 14 presenting as language delay. Am J Hum Genet. 2001; 69: 309.
- Temple IK, Cockwell A, Hassold T, Pettay D, Jacobs P. Maternal uniparental disomy for chromosome 14. J Med Genet. 1991; 28: 511-514. [CrossRef]
- Berends MJ, Hordijk R, Scheffer H, Oosterwijk JC, Halley DJ, Sorgedrager N. Two cases of maternal uniparental disomy 14 with a phenotype overlapping with the Prader-Willi phenotype. Am J Med Genet. 1999; 84: 76-79. [CrossRef]
- Coviello DA, Panucci E, Mantero MM, Perfumo C, Guelfi M, Borrone C, et al. Maternal uniparental disomy for chromosome 14. Acta Genet Med Gemellol. 1996; 45: 169-172. [CrossRef]
- Desilets VA, Yong SL, Kalousek DK, Pantzer TJ, Kwong LC, Siemens C, et al. Maternal uniparental disomy for chromosome 14. Am J Hum Genet. 1997; 61: 691.
- Giunti L, Lapi E, Guarducci S, Ricci U, Cecconi A, Andreucci E, et al. Maternal heterodisomy for chromosome 14 and 13/14 Robertsonian translocation in a female with normal mental development, short stature and dysmorphic features. Eur J Hum Genet. 2002; 10: 120.
- Healey S, Powell F, Battersby M, Chenevix-Trench G, McGill J. Distinct phenotype in maternal uniparental disomy of chromosome 14. Am J Med Genet. 1994; 51: 147-149. [CrossRef]
- Krabchi K, Ferland M, Halal F, Russel L, Duncan AMV, Drouin R. Unusual clinical features observed in a young girl having an inherited maternal translocation (13;14) with a mixed maternal uniparental hetero and isodisomy. Am J Hum Genet. 2005; 77: abstract 843.
- Ruggeri A, Dulcetti F, Miozzo M, Grati FR, Grimi B, Bellato S, et al. Prenatal search for UPD 14 and UPD 15 in 83 cases of familial and de novo heterologous Robertsonian translocations. Prenat Diagn. 2004; 24: 997-1000. [CrossRef]
- Sensi A, Cavani S, Villa N, Pomponi MG, Fogli A, Gualandi F, et al. Nonhomologous Robertsonian translocations (NHRTs) and uniparental disomy (UPD) risk: An Italian multicentric prenatal survey. Prenat Diagn. 2004; 24: 647-652. [CrossRef]
- Takahashi I, Takahashi T, Utsunomiya M, Takada G, Koizumi A. Long-acting gonadotropin-releasing hormone analogue treatment for central precocious puberty in maternal uniparental disomy chromosome 14. Tohoku J Exp Med. 2005; 207: 333-338. [CrossRef]
- Falk MJ, Curtis CA, Bass NE, Zinn AB, Schwartz S. Maternal uniparental disomy chromosome 14: Case report and literature review. Pediatr Neurol. 2005; 32: 116-120. [CrossRef]
- Manzoni MF, Pramparo T, Stroppolo A, Chiaino F, Bosi E, Zuffardi O, et al. A patient with maternal chromosome 14 UPD presenting with a mild phenotype and MODY. Clin Genet. 2000; 57: 406-408. [CrossRef]
- Miyoshi O, Hayashi S, Fujimoto M, Tomita H, Sohda M, Niikawa N. Maternal uniparental disomy for chromosome 14 in a boy with intrauterine growth retardation. J Hum Genet. 1998; 43: 138-142. [CrossRef]
- Tomkins DJ, Roux AF, Waye J, Freeman VC, Cox DW, Whelan DT. Maternal uniparental isodisomy of human chromosome 14 associated with a paternal t(13q14q) and precocious puberty. Eur J Hum Genet. 1996; 4: 153-159. [CrossRef]
- Papenhausen PR, Tepperberg JH, Mowrey PN, Gadi IK, Shah HO, Sherman J, et al. UPD risk assessment: Three cytogenetic subgroups. Am J Hum Genet. 1999; 65: A353.
- Splitt MP, Goodship JA. Another case of maternal uniparental disomy chromosome 14 syndrome. Am J Med Genet. 1997; 72: 239-240. [CrossRef]
- Stucke-Sontheimer A, Chaoui R, Unger M, Ramel C, von Eggeling F, Thiel G, et al. Fetal left isomerism (polysplenia) and maternal uniparental disomy 14: Evidence for a recessive gene for heterotaxia on chromosome 14? Medgen. 2007; 18: 68.
- Pentao L, Lewis RA, Ledbetter DH, Patel PI, Lupski JR. Maternal uniparental isodisomy of chromosome 14: Association with autosomal recessive rod monochromacy. Am J Hum Genet. 1992; 50: 690-699.
- Wang X, Pang H, Shah BA, Gu H, Zhang L, Wang H. A male case of Kagami-Ogata syndrome caused by paternal unipaternal disomy 14 as a result of a Robertsonian translocation. Front Pediatr. 2020; 8: 88. [CrossRef]
- Cotter PD, Kaffe S, McCurdy LD, Jhaveri M, Willner JP, Hirschhorn K. Paternal uniparental disomy for chromosome 14: A case report and review. Am J Med Genet. 1997; 70: 74-79. [CrossRef]
- Igreja da Silva JI, Ribeiro B, Cadilhe A, Nogueira-Silva C. Paternal uniparental disomy for chromosome 14: Prenatal management. BMJ Case Rep. 2019; 12: e231705. [CrossRef]
- Kurosawa K, Sasaki H, Sato Y, Yamanaka M, Shimizu M, Ito Y, et al. Paternal UPD14 is responsible for a distinctive malformation complex. Am J Med Genet. 2002; 110: 268-272. [CrossRef]
- Ogata T, Kagami M. Kagami-Ogata syndrome: A clinically recognizable UPD(14)pat and related disorder affecting the chromosome 14q32.2 imprinted region. J Hum Genet. 2016; 61: 87-94. [CrossRef]
- Wang JC, Passage MB, Yen PH, Shapiro LJ, Mohandas TK. Uniparental heterodisomy for chromosome 14 in a phenotypically abnormal familial balanced 13/14 Robertsonian translocation carrier. Am J Hum Genet. 1991; 48: 1069-1074.
- Yano S, Li L, Owen S, Wu S, Tran T. A further delineation of the paternal uniparental disomy (UPD) 14: The fifth reported case. Am J Hum Genet. 2001; 69: 739.
- Walter CA, Shaffer LG, Kaye CI, Huff RW, Ghidoni PD, McCaskill C, et al. Short-limb dwarfism and hypertrophic cardiomyopathy in a patient with paternal isodisomy 14: 45,XY,idic(14)(p11). Am J Med Genet. 1996; 65: 259-265. [CrossRef]
- Klein J, Shaffer LG, McCaskill C, Scheere L, Otto L, Main D, et al. Delineation of the paternal disomy 14 syndrone: Identification of a case by prenatal diagnosis. Am J Hum Genet. 1999; 65: A179.
- Stevenson DA, Brothman AR, Chen Z, Bayrak-Toydemir P, Longo N. Paternal uniparental disomy of chromosome 14: Confirmation of a clinically-recognizable phenotype. Am J Med Genet A. 2004; 130: 88-91. [CrossRef]
- McGowan KD, Weiser JJ, Horwitz J, Berend SA, McCaskill C, Sutton VR, et al. The importance of investigating for uniparental disomy in prenatally identified balanced acrocentric rearrangements. Prenat Diagn. 2002; 22: 141-143. [CrossRef]
- Kovaleva NV, Shaffer LG. Under-ascertainment of mosaic carriers of balanced homologous acrocentric translocations and isochromosomes. Am J Med Genet A. 2003; 121: 180-187. [CrossRef]
- Stetten G, Tuck-Muller CM, Blakemore KJ, Wong C, Kazazian HH Jr, Antonarakis SE. Evidence for involvement of a Robertsonian translocation 13 chromosome in formation of a ring chromosome 13. Mol Biol Med. 1990; 7: 479-484.
- Adam LR, Kashork CD, Van den Veyver IB, Sutton VR, Bacino CA, Shaffer LG. Ring chromosome 15: Discordant karyotypes in amniotic fluid, placenta and cord. Am J Hum Genet. 1998; 63: A126.
- Quiroga R, Roselló M, Martinez F, Ferrer-Bolufer I, Monfort S, Oltra S, et al. Rare chromosomal complement of trisomy 21 in a boy conceived by IVF and cryopreservation. Reprod Biomed Online. 2009; 19: 415-417. [CrossRef]
- Souraty N, Sanlaville D, Chédid R, Le Lorc'h M, Maurin ML, Ghanem L, et al. Cytogenetic investigation of a child with a mosaic isochromosome 18q and ring 18q. Eur J Med Genet. 2007; 50: 379-385. [CrossRef]
- Akin H, Karaca E, Hortu I, Bolat H, Cengisiz Z, Kazandi M, et al. Cytogenetic analysis of miscarriage materials of couples with recurrent pregnancy loss in a tertiary center. Clin Exp Obstet Gynecol. 2019; 46: 423-426. [CrossRef]
- Babu R, Van Dyke DL, Bhattacharya S, Dev VG, Liu M, Kwon M, et al. A rapid and reliable chromosome analysis method for products of conception using interphase nuclei. Mol Genet Genomic Med. 2018; 6: 370-381. [CrossRef]
- Baxter L, Adayapalam N. A comparative study of standard cytogenetic evaluation and molecular karyotyping for products of conception. Diagn Mol Pathol. 2013; 22: 228-235. [CrossRef]
- Boué J, Daketsé MJ, Deluchat C, Ravisé N, Yvert F, Boué A. Identification by Q and G bands of chromosome anomalies in spontaneous abortion. Ann Genet. 1976; 19: 233-239.
- Bruno DL, Burgess T, Ren H, Nouri S, Pertile MD, Francis DI, et al. High-throughput analysis of chromosome abnormality in spontaneous miscarriage using an MLPA subtelomere assay with an ancillary FISH test for polyploidy. Am J Med Genet. 2006; 140: 2786-2793. [CrossRef]
- Carr DH, Gedeon MM. Q-banding of chromosomes in human spontaneous abortions. Can J Genet Cytol. 1978; 20: 415-425. [CrossRef]
- Causio F, Fischetto R, Sarcina E, Geusa S, Tartagni M. Chromosome analysis of spontaneous abortions after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Eur J Obstet Gynecol Reprod Biol. 2002; 105: 44-48. [CrossRef]
- Gimovsky AC, Pham A, Moreno SC, Nicholas S, Roman A, Weiner S. Genetic abnormalities seen on CVS in early pregnancy failure. J Matern Fetal Neonatal Med. 2020; 33: 2142-2147. [CrossRef]
- Guerneri S, Bettio D, Simoni G, Brambati B, Lanzani A, Fraccaro M. Prevalence and distribution of chromosome abnormalities in a sample of first trimester internal abortions. Hum Reprod. 1987; 2: 735-739. [CrossRef]
- Wilson C, Yamane JA, Jacobs PA. A cytogenetic study of 1000 spontaneous abortions. Ann Hum Genet. 1980; 44: 151-178. [CrossRef]
- Jacobs PA, Hassold TJ, Henry A, Pettay D, Takaesu N. Trisomy 13 ascertained in a survey of spontaneous abortions. J Med Genet. 1987; 24: 721-724. [CrossRef]
- Horiuchi I, Wakimoto Y, Kuwata T, Sawai H, Shibahara H, Takagi K. Cytogenetic analysis of spontaneous miscarriages using long-term culturing of chorionic villi. J Fetal Med. 2019; 6: 1-6. [CrossRef]
- Kajii T, Ferrier A, Niikawa N, Takahara H, Ohama K, Avirachan S. Anatomic and chromosomal anomalies in 639 spontaneous abortuses. Hum Genet. 1980; 55: 87-98. [CrossRef]
- Karaoguz MY, Nas T, Konaç E, Ince D, Pala E, Menevse S. Is cytogenetic diagnosis of 46,XX karyotype spontaneous abortion specimens erroneous? Fluorescence in situ hybridization as a confirmatory technique. J Obstet Gynaecol Res. 2005; 31: 508-513. [CrossRef]
- Lauritsen JG. Aetiology of spontaneous abortion: A cytogenetic and epidemiological study of 288 abortuses and their parents. Acta Obstet Gynecol Scand. 1976; 55: 1-29. [CrossRef]
- Lin CC, De Braekeleer M, Jamro H. Cytogenetic studies in spontaneous abortion: The Calgary experience. Can J Genet Cytol. 1985; 27: 565-570. [CrossRef]
- Ljunger E, Cnattingius S, Lundin C, Annerén G. Chromosomal anomalies in first-trimester miscarriages. Acta Obstet Gynecol Scand. 2005; 84: 1103-1107. doi: 10.1111/j.0001-6349.2005.00882.x. [CrossRef]
- Ma S, Philipp T, Zhao Y, Stetten G, Robinson WP, Kalousek D. Frequency of chromosomal abnormalities in spontaneous abortions derived from intracytoplasmic sperm injection compared with those from in vitro fertilization. Fertil Steril. 2006; 85: 236-239. [CrossRef]
- Ocak Z, Özlü T, Ozyurt O. Association of recurrent pregnancy loss with chromosomal abnormalities and hereditary thrombophilias. Afr Health Sci. 2013; 13: 447-452. [CrossRef]
- Ohno M, Maeda T, Matsunobu A. A cytogenetic study of spontaneous abortions with direct analysis of chorionic villi. Obstet Gynecol. 1991; 77: 394-398.
- Robberecht C, Schuddinck V, Fryns JP, Vermeesch JR. Diagnosis of miscarriages by molecular karyotyping: Benefits and pitfalls. Genet Med. 2009; 11: 646-654. [CrossRef]
- Robinson WP, McFadden DE, Stephenson MD. The origin of abnormalities in recurrent aneuploidy/polyploidy. Am J Hum Genet. 2001; 69: 1245-1254. [CrossRef]
- Schaeffer AJ, Chung J, Heretis K, Wong A, Ledbetter DH, Lese Martin C. Comparative genomic hybridization-array analysis enhances the detection of aneuploidies and submicroscopic imbalances in spontaneous miscarriages. Am J Hum Genet. 2004; 74: 1168-1174. [CrossRef]
- Soler A, Morales C, Mademont-Soler I, Margarit E, Borrell A, Borobio V, et al. Overview of chromosome abnormalities in first trimester miscarriages: A series of 1,011 consecutive chorionic villi sample karyotypes. Cytogenet Genome Res. 2017; 152: 81-89. [CrossRef]
- Strom CM, Ginsberg N, Applebaum M, Bozorgi N, White M, Caffarelli M, et al. Analyses of 95 first-trimester spontaneous abortions by chorionic villus sampling and karyotype. J Assist Reprod Genet. 1992; 9: 458-461. [CrossRef]
- Veropotvelyan NP, Poguliay YS, Savarovskaya ES. Prevalence and spectrum of chromosome abnormalities among spontaneous and induced early reproductive losses: 2020 miscarriages and 1572 medical abortions. Reprod Endocrinol. 2020; 55: 8-19. [CrossRef]
- Jenderny J. Chromosome aberrations in a large series of spontaneous miscarriages in the German population and review of the literature. Mol Cytogenet. 2014; 7: 38. doi: 10.1186/1755-8166-7-38. [CrossRef]
- Lebedev N, Ostroverkhova NV, Nikitina TV, Sukhanova NN, Nazerenko SA. Features of chromosomal abnormalities in spontaneous abortion cell culture failures detected by interphase FISH analysis. Eur J Hum Genet. 2004; 12: 513-520. [CrossRef]
- Kovaleva NV. Sex-specific chromosome instability in early human development. Am J Med Genet A. 2005; 136: 401-413. [CrossRef]
- Kovaleva NV. An overlooked phenomenon: Female-biased sex ratio among carriers of robertsonian translocations detected in consecutive newborn studies. Russ J Genet. 2017; 53: 1366-1373. [CrossRef]
- Kovaleva NV, Cotter PD. Mosaicism for structural non-centromeric autosomal rearrangement in prenatal diagnoses: Evidence for sex-specific selection against chromosomal abnormalities. Mol Cytogenet. 2017; 10: 45. [CrossRef]
- Kotzot D. Advanced parental age in maternal uniparental disomy (UPD): Implications for the mechanism of formation. Eur J Hum Genet. 2004; 12: 343-346. [CrossRef]
- Nadă ES, Albu DF, Pătraşcu A, Albu ŞD, Gogănău AM, Albu CC. Current opportunities and new horizons into the genetic study of infertility. Rom J Morphol Embryol. 2021; 62: 191-200. [CrossRef]
- Kovaleva NV. Germ-line transmission of trisomy 21: Data from 80 families suggest an implication of grandmaternal age and a high frequency of female-specific trisomy rescue. Mol Cytogenet. 2010; 3: 7. [CrossRef]