A cluster of autosomal recessive spondylocostal dysostosis caused by three newly identified DLL3 mutations segregating in a small village
Details
Serval ID
serval:BIB_5982EEFE3A6E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A cluster of autosomal recessive spondylocostal dysostosis caused by three newly identified DLL3 mutations segregating in a small village
Journal
Clinical Genetics
ISSN
0009-9163
Publication state
Published
Issued date
07/2003
Peer-reviewed
Oui
Volume
64
Number
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
Abstract
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.
Keywords
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
Create date
21/01/2008 13:50
Last modification date
20/08/2019 15:13