Angelman syndrome with mosaic paternal uniparental disomy suggestive of mitotic nondisjunction.
Journal
Journal of human genetics
ISSN: 1435-232X
Titre abrégé: J Hum Genet
Pays: England
ID NLM: 9808008
Informations de publication
Date de publication:
Feb 2023
Feb 2023
Historique:
received:
25
07
2022
accepted:
27
09
2022
revised:
15
09
2022
pubmed:
13
10
2022
medline:
27
1
2023
entrez:
12
10
2022
Statut:
ppublish
Résumé
Angelman syndrome (AS) is caused by the functional absence of the maternal ubiquitin-protein ligase E3A (UBE3A) gene. Approximately 5% of AS is caused by paternal uniparental disomy of chromosome 15 (UPD(15)pat), most of which is considered to result from monosomy rescue. However, little attention has focused on how UPD(15)pat occurs. We suggest the mitotic nondisjunction mechanism as a cause of UPD(15)pat in a six-year-old patient presenting with distinctive characteristics in line with AS. DNA methylation screening of 15q11-q13 showed a paternal band and a faint maternal band, suggestive of mosaic status. By trio-based microsatellite analysis, we confirmed a large proportion of UPD(15)pat cells and a small proportion of cells of biparental origin. Single nucleotide polymorphism (SNP) microarray revealed isodisomy of the entire chromosome 15. These results suggest that the UPD(15)pat of the patient resulted from mitotic nondisjunction, which may also be the cause of other cases of AS with UPD(15)pat.
Identifiants
pubmed: 36224263
doi: 10.1038/s10038-022-01088-z
pii: 10.1038/s10038-022-01088-z
doi:
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
87-90Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s), under exclusive licence to The Japan Society of Human Genetics.
Références
Buiting K, Williams C, Horsthemke B. Angelman syndrome - insights into a rare neurogenetic disorder. Nat Rev Neurol. 2016;12:584–93.
doi: 10.1038/nrneurol.2016.133
Tan WH, Bacino CA, Skinner SA, Anselm I, Barbieri-Welge R, Bauer-Carlin A, et al. Angelman syndrome: Mutations influence features in early childhood. Am J Med Genet. 2011;155:81–90.
doi: 10.1002/ajmg.a.33775
Robinson WP, Christian SL, Kuchinka BD, Peñaherrera MS, Das S, Schuffenhauer S, et al. Somatic segregation errors predominantly contribute to the gain or loss of a paternal chromosome leading to uniparental disomy for chromosome 15. Clin Genet. 2000;57:349–58.
doi: 10.1034/j.1399-0004.2000.570505.x
Martin RH, Ko E, Rademaker A. Distribution of aneuploidy in human gametes: Comparison between human sperm and oocytes. Am J Med Genet. 1991;39:321–31.
doi: 10.1002/ajmg.1320390315
Yamazawa K, Ogata T, Ferguson-Smith AC. Uniparental disomy and human disease: An overview. Am J Med Genet Part C Semin Med Genet. 2010;154:329–34.
doi: 10.1002/ajmg.c.30270
Kubota T, Das S, Christian SL, Baylin SB, Herman JG, Ledbetter DH. Methylation-specific PCR simplifies imprinting analysis. Nat Genet. 1997;16:16–17.
doi: 10.1038/ng0597-16
Saitoh S, Wada T, Okajima M, Takano K, Sudo A, Niikawa N. Uniparental disomy and imprinting defects in Japanese patients with Angelman syndrome. Brain Dev. 2005;27:389–91.
doi: 10.1016/j.braindev.2003.12.013
Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010;86:749–64.
doi: 10.1016/j.ajhg.2010.04.006
Chen CP, Chern SR, Chen YN, Wu PS, Yang CW, Chen LF, et al. Mosaic trisomy 15 at amniocentesis: Prenatal diagnosis, molecular genetic analysis and literature review. Taiwan J Obstet Gynecol. 2015;54:426–31.
doi: 10.1016/j.tjog.2015.06.002
Morandi A, Bonnefond A, Lobbens S, Carotenuto M, del Giudice EM, Froguel P, et al. A girl with incomplete Prader-Willi syndrome and negative MS-PCR, found to have mosaic maternal UPD-15 at SNP array. Am J Med Genet. 2015;167:2720–6.
doi: 10.1002/ajmg.a.37222
Carson RP, Bird L, Childers AK, Wheeler F, Duis J. Preserved expressive language as a phenotypic determinant of Mosaic Angelman Syndrome. Mol Genet Genom Med. 2019;7:1–10.
Narayanan DL, Ranganath P, Balakrishnan S, Dalal A. Mosaic paternal uniparental isodisomy of 15q11-q13 region causing Angelman phenotype. Clin Dysmorphol. 2019;28:202–4.
doi: 10.1097/MCD.0000000000000284