Exome Sequencing Identifies INPPL1 Mutations as a Cause of Opsismodysplasia.

Détails

ID Serval
serval:BIB_70E3F45EC7E0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Exome Sequencing Identifies INPPL1 Mutations as a Cause of Opsismodysplasia.
Périodique
American Journal of Human Genetics
Auteur(s)
Huber C., Faqeih E.A., Bartholdi D., Bole-Feysot C., Borochowitz Z., Cavalcanti D.P., Frigo A., Nitschke P., Roume J., Santos H.G., Shalev S.A., Superti-Furga A., Delezoide A.L., Le Merrer M., Munnich A., Cormier-Daire V.
ISSN
1537-6605 (Electronic)
ISSN-L
0002-9297
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
92
Numéro
1
Pages
144-149
Langue
anglais
Notes
Publication types: Journal Article
Résumé
Opsismodysplasia (OPS) is a severe autosomal-recessive chondrodysplasia characterized by pre- and postnatal micromelia with extremely short hands and feet. The main radiological features are severe platyspondyly, squared metacarpals, delayed skeletal ossification, and metaphyseal cupping. In order to identify mutations causing OPS, a total of 16 cases (7 terminated pregnancies and 9 postnatal cases) from 10 unrelated families were included in this study. We performed exome sequencing in three cases from three unrelated families and only one gene was found to harbor mutations in all three cases: inositol polyphosphate phosphatase-like 1 (INPPL1). Screening INPPL1 in the remaining cases identified a total of 12 distinct INPPL1 mutations in the 10 families, present at the homozygote state in 7 consanguinous families and at the compound heterozygote state in the 3 remaining families. Most mutations (6/12) resulted in premature stop codons, 2/12 were splice site, and 4/12 were missense mutations located in the catalytic domain, 5-phosphatase. INPPL1 belongs to the inositol-1,4,5-trisphosphate 5-phosphatase family, a family of signal-modulating enzymes that govern a plethora of cellular functions by regulating the levels of specific phosphoinositides. Our finding of INPPL1 mutations in OPS, a severe spondylodysplastic dysplasia with major growth plate disorganization, supports a key and specific role of this enzyme in endochondral ossification.
Pubmed
Web of science
Open Access
Oui
Création de la notice
23/01/2013 10:44
Dernière modification de la notice
20/08/2019 14:29
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