Relative Frequency of Underlying Genetic Causes for the Development of UPD(14)pat-like Phenotype

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2012 Feb 23

PMID 22353941

Citations 20

Authors

Masayo Kagami

Fumiko Kato

Keiko Matsubara

Tomoko Sato

Gen Nishimura

Tsutomu Ogata

Affiliations

Soon will be listed here.

Abstract

Paternal uniparental disomy 14 (UPD(14)pat) results in a unique constellation of clinical features, and a similar phenotypic constellation is also caused by microdeletions involving the DLK1-MEG3 intergenic differentially methylated region (IG-DMR) and/or the MEG3-DMR and by epimutations (hypermethylations) affecting the DMRs. However, relative frequency of such underlying genetic causes remains to be clarified, as well as that of underlying mechanisms of UPD(14)pat, that is, trisomy rescue (TR), gamete complementation (GC), monosomy rescue (MR), and post-fertilization mitotic error (PE). To examine this matter, we sequentially performed methylation analysis, microsatellite analysis, fluorescence in situ hybridization, and array-based comparative genomic hybridization in 26 patients with UPD(14)pat-like phenotype. Consequently, we identified UPD(14)pat in 17 patients (65.4%), microdeletions of different patterns in 5 patients (19.2%), and epimutations in 4 patients (15.4%). Furthermore, UPD(14)pat was found to be generated through TR or GC in 5 patients (29.4%), MR or PE in 11 patients (64.7%), and PE in 1 patient (5.9%). Advanced maternal age at childbirth (≥35 years) was predominantly observed in the MR/PE subtype. The results imply that the relative frequency of underlying genetic causes for the development of UPD(14)pat-like phenotype is different from that of other imprinting disorders, and that advanced maternal age at childbirth as a predisposing factor for the generation of nullisomic oocytes through non-disjunction at meiosis 1 may be involved in the development of MR-mediated UPD(14)pat.

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References

Matsubara K, Murakami N, Nagai T, Ogata T . Maternal age effect on the development of Prader-Willi syndrome resulting from upd(15)mat through meiosis 1 errors. J Hum Genet. 2011; 56(8):566-71. DOI: 10.1038/jhg.2011.59. View

Towner D, Shaffer L, Yang S, Walgenbach D . 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(5):395-8. DOI: 10.1002/pd.75. View

Kagami M, Nishimura G, Okuyama T, Hayashidani M, Takeuchi T, Tanaka S . Segmental and full paternal isodisomy for chromosome 14 in three patients: narrowing the critical region and implication for the clinical features. Am J Med Genet A. 2005; 138A(2):127-32. DOI: 10.1002/ajmg.a.30941. View

Eggermann T . Epigenetic regulation of growth: lessons from Silver-Russell syndrome. Endocr Dev. 2009; 14:10-9. DOI: 10.1159/000207472. View

Varela M, Kok F, Setian N, Kim C, Koiffmann C . Impact of molecular mechanisms, including deletion size, on Prader-Willi syndrome phenotype: study of 75 patients. Clin Genet. 2004; 67(1):47-52. DOI: 10.1111/j.1399-0004.2005.00377.x. View

Kagami M, OSullivan M, Green A, Watabe Y, Arisaka O, Masawa N . The IG-DMR and the MEG3-DMR at human chromosome 14q32.2: hierarchical interaction and distinct functional properties as imprinting control centers. PLoS Genet. 2010; 6(6):e1000992. PMC: 2887472. DOI: 10.1371/journal.pgen.1000992. View

Sanlaville D, Aubry M, Dumez Y, Nolen M, Amiel J, Pinson M . Maternal uniparental heterodisomy of chromosome 14: chromosomal mechanism and clinical follow up. J Med Genet. 2000; 37(7):525-8. PMC: 1734622. DOI: 10.1136/jmg.37.7.525. View

Hordijk R, Wierenga H, Scheffer H, Leegte B, Hofstra R, Stolte-Dijkstra I . Maternal uniparental disomy for chromosome 14 in a boy with a normal karyotype. J Med Genet. 1999; 36(10):782-5. PMC: 1734247. DOI: 10.1136/jmg.36.10.782. View

Fokstuen S, Ginsburg C, ZACHMANN M, Schinzel A . Maternal uniparental disomy 14 as a cause of intrauterine growth retardation and early onset of puberty. J Pediatr. 1999; 134(6):689-95. DOI: 10.1016/s0022-3476(99)70282-9. View

10.

Robinson W, Christian S, Kuchinka B, Penaherrera M, Das S, Schuffenhauer S . Somatic segregation errors predominantly contribute to the gain or loss of a paternal chromosome leading to uniparental disomy for chromosome 15. Clin Genet. 2000; 57(5):349-58. DOI: 10.1034/j.1399-0004.2000.570505.x. View

11.

Sasaki K, Soejima H, Higashimoto K, Yatsuki H, Ohashi H, Yakabe S . Japanese and North American/European patients with Beckwith-Wiedemann syndrome have different frequencies of some epigenetic and genetic alterations. Eur J Hum Genet. 2007; 15(12):1205-10. DOI: 10.1038/sj.ejhg.5201912. View

12.

Kagami M, Sekita Y, Nishimura G, Irie M, Kato F, Okada M . Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes. Nat Genet. 2008; 40(2):237-42. DOI: 10.1038/ng.2007.56. View

13.

Aretz S, Raff R, Woelfle J, Zerres K, Esser M, Propping P . Maternal uniparental disomy 14 in a 15-year-old boy with normal karyotype and no evidence of precocious puberty. Am J Med Genet A. 2005; 135(3):336-8. DOI: 10.1002/ajmg.a.30755. View

14.

Kotzot D . Advanced parental age in maternal uniparental disomy (UPD): implications for the mechanism of formation. Eur J Hum Genet. 2004; 12(5):343-6. DOI: 10.1038/sj.ejhg.5201158. View

15.

Hoffmann K, Heller R . Uniparental disomies 7 and 14. Best Pract Res Clin Endocrinol Metab. 2011; 25(1):77-100. DOI: 10.1016/j.beem.2010.09.004. View

16.

Cotter P, Kaffe S, McCurdy L, Jhaveri M, Willner J, Hirschhorn K . Paternal uniparental disomy for chromosome 14: a case report and review. Am J Med Genet. 1997; 70(1):74-9. DOI: 10.1002/(sici)1096-8628(19970502)70:1<74::aid-ajmg14>3.0.co;2-u. View

17.

Shaffer L, Agan N, Goldberg J, Ledbetter D, Longshore J, Cassidy S . American College of Medical Genetics statement of diagnostic testing for uniparental disomy. Genet Med. 2001; 3(3):206-11. PMC: 3111049. DOI: 10.1097/00125817-200105000-00011. View

18.

McGowan K, Weiser J, Horwitz J, Berend S, McCaskill C, Sutton V . The importance of investigating for uniparental disomy in prenatally identified balanced acrocentric rearrangements. Prenat Diagn. 2002; 22(2):141-3. View

19.

Mitter D, Buiting K, von Eggeling F, Kuechler A, Liehr T, Mau-Holzmann U . 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 A. 2006; 140(19):2039-49. DOI: 10.1002/ajmg.a.31414. View

20.

Wang J, Passage M, Yen P, Shapiro L, Mohandas T . Uniparental heterodisomy for chromosome 14 in a phenotypically abnormal familial balanced 13/14 Robertsonian translocation carrier. Am J Hum Genet. 1991; 48(6):1069-74. PMC: 1683099. View