FXS-Like Phenotype in Two Unrelated Patients Carrying a Methylated Premutation of the <i>FMR1</i> Gene.

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Version: Final published version
Serval ID
serval:BIB_CA961EE72B81
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
FXS-Like Phenotype in Two Unrelated Patients Carrying a Methylated Premutation of the <i>FMR1</i> Gene.
Journal
Frontiers in Genetics
Author(s)
Fernández E., Gennaro E., Pirozzi F., Baldo C., Forzano F., Turolla L., Faravelli F., Gastaldo D., Coviello D., Grasso M., Bagni C.
ISSN
1664-8021 (Print)
ISSN-L
1664-8021
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
9
Pages
442
Language
english
Abstract
Fragile X syndrome (FXS) is mostly caused by two distinct events that occur in the <i>FMR1</i> gene (Xq27.3): an expansion above 200 repeats of a CGG triplet located in the 5'UTR of the gene, and methylation of the cytosines located in the CpG islands upstream of the CGG repeats. Here, we describe two unrelated families with one FXS child and another sibling presenting mild intellectual disability and behavioral features evocative of FXS. Genetic characterization of the undiagnosed sibling revealed mosaicism in both the CGG expansion size and the methylation levels in the different tissues analyzed. This report shows that in the same family, two siblings carrying different CGG repeats, one in the full-mutation range and the other in the premutation range, present methylation mosaicism and consequent decreased FMRP production leading to FXS and FXS-like features, respectively. Decreased FMRP levels, more than the number of repeats seem to correlate with the severity of FXS clinical phenotypes.
Keywords
CGG expansion, FMR1 mRNA, FMRP, fragile X syndrome, mosaicism
Pubmed
Web of science
Open Access
Yes
Create date
22/11/2018 9:26
Last modification date
20/08/2019 16:45
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