Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia.

Details

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State: Serval
Version: Final published version
Serval ID
serval:BIB_825739ACCA7E
Type
Article: article from journal or magazin.
Collection
Publications
Title
Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia.
Journal
Scientific Reports
Author(s)
Royer-Bertrand B., Castillo-Taucher S., Moreno-Salinas R., Cho T.J., Chae J.H., Choi M., Kim O.H., Dikoglu E., Campos-Xavier B., Girardi E., Superti-Furga G., Bonafé L., Rivolta C., Unger S., Superti-Furga A.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
5
Pages
17154
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
We and others have reported mutations in LONP1, a gene coding for a mitochondrial chaperone and protease, as the cause of the human CODAS (cerebral, ocular, dental, auricular and skeletal) syndrome (MIM 600373). Here, we delineate a similar but distinct condition that shares the epiphyseal, vertebral and ocular changes of CODAS but also included severe microtia, nasal hypoplasia, and other malformations, and for which we propose the name of EVEN-PLUS syndrome for epiphyseal, vertebral, ear, nose, plus associated findings. In three individuals from two families, no mutation in LONP1 was found; instead, we found biallelic mutations in HSPA9, the gene that codes for mHSP70/mortalin, another highly conserved mitochondrial chaperone protein essential in mitochondrial protein import, folding, and degradation. The functional relationship between LONP1 and HSPA9 in mitochondrial protein chaperoning and the overlapping phenotypes of CODAS and EVEN-PLUS delineate a family of "mitochondrial chaperonopathies" and point to an unexplored role of mitochondrial chaperones in human embryonic morphogenesis.
Keywords
Abnormalities, Multiple/genetics, Abnormalities, Multiple/radiography, Bone Diseases, Developmental/genetics, Bone Diseases, Developmental/radiography, Child, Preschool, DNA Mutational Analysis, Female, Genetic Association Studies, HSP70 Heat-Shock Proteins/genetics, Humans, Mitochondrial Proteins/genetics, Musculoskeletal Abnormalities/genetics, Musculoskeletal Abnormalities/radiography, Mutation, Missense, Syndrome
Pubmed
Web of science
Open Access
Yes
Create date
15/12/2015 18:33
Last modification date
08/05/2019 21:12
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