Ethnicity has a multiplex impact upon the risk of a full mutation expansion among female heterozygotes for FMR1 premutation.
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
23
08
2020
accepted:
21
12
2020
revised:
21
12
2020
pubmed:
22
1
2021
medline:
8
7
2021
entrez:
21
1
2021
Statut:
ppublish
Résumé
To evaluate whether ethnicity affects the risk of full mutation expansion among females heterozygous for FMR1 premutation. Women who carry the FMR1 premutation alelle of Jewish origin who underwent fragile X prenatal diagnosis between 2011 and 2018 in two medical centers in Israel were included. The heterozygote women and fetuses were analyzed for the number of CGG repeats and AGG interruptions. Seven hundred sixty-six subjects were included. Parental ethnicity was fully concordant in 592 cases (Jewish, Ashkenazi, and non-Ashkenazi). Ashkenazi compared with non-Ashkenazi heterozygotes have a significantly higher mean number of CGG repeats (68 ± 8.7, 64 ± 6.4 respectively, P = 0.03) and a lower mean number of AGG interruptions (0.89 ± 0.83, 1.60 ± 1.18 respectively, p = 0.0001). Overall, 56/198 (28.2%) fetuses of Ashkenazi heterozygotes had an expansion to a full mutation compared with 6/98 among the non-Ashkenazi (6.1%) (p = 0.001). Multivariate analysis demonstrated that, in addition to CGG repeats and AGG interruptions (which contributed 68.3% of variance), ethnicity is an independent risk factor for a full mutation expansion (odds ratio [OR] = 2.04, p < 0.001) and accounted for 9% of the variation of a full mutation expansion. Apart from significant differences regarding the number of CGG repeats and AGG interruptions between Ashkenazi and non-Ashkenazi heterozygotes, ethnicity independently affects the risk of a full mutation.
Identifiants
pubmed: 33473206
doi: 10.1038/s41436-020-01089-3
pii: S1098-3600(21)05204-7
doi:
Substances chimiques
FMR1 protein, human
0
Fragile X Mental Retardation Protein
139135-51-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1023-1027Références
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