A cluster of autosomal recessive spondylocostal dysostosis caused by three newly identified DLL3 mutations segregating in a small village
Détails
ID Serval
serval:BIB_5982EEFE3A6E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A cluster of autosomal recessive spondylocostal dysostosis caused by three newly identified DLL3 mutations segregating in a small village
Périodique
Clinical Genetics
ISSN
0009-9163
Statut éditorial
Publié
Date de publication
07/2003
Peer-reviewed
Oui
Volume
64
Numéro
1
Pages
28-35
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jul
Research Support, Non-U.S. Gov't --- Old month value: Jul
Résumé
In 1982, one of us reported a cluster of eight individuals affected by spondylocostal dysostosis (SD, MIM 277300) in four nuclear families indigenous to a village from eastern Switzerland. We tested the hypothesis that the molecular basis for this cluster was segregation of a single mutation in the DLL3 gene, recently linked to SD. Marker haplotypes around the DLL3 locus contradicted this hypothesis as three different haplotypes were seen in affected individuals, but sequence analysis showed that three unreported DLL3 mutations were segregating: a duplication of 17 bp in exon 8 (c.1285-1301dup), a single-nucleotide deletion in exon 5 (c.615delC), and a R238X nonsense mutation in exon 6. Contrary to our initial assumption of a single allele segregating in this small community, three different pathogenic alleles were observed, with a putative founder mutation occurring at the homozygous state but also compounding with, and thus revealing, two other independent mutations. As all three mutations predict truncation of the DLL3 protein and loss of the membrane-attaching domain, the results confirm that autosomal recessive spondylocostal dysostosis represents the null phenotype of DLL3, with remarkable phenotypic consistency across families.
Mots-clé
Dysostoses/*genetics
Female
Founder Effect
Genes, Recessive
Humans
Linkage (Genetics)
Male
Membrane Proteins/*genetics
Mutation
Pedigree
Protein Structure, Tertiary
Ribs/abnormalities/radiography
Sequence Analysis, DNA
Spine/abnormalities/radiography
Pubmed
Web of science
Création de la notice
21/01/2008 13:50
Dernière modification de la notice
20/08/2019 15:13