Abstract:
:In spondylocostal dysostosis (SD), vertebral-segmentation defects are associated with rib anomalies. This results in short-trunk short stature, nonprogressive kyphoscoliosis, and radiological features of multiple hemivertebrae and rib fusions. SD can be familial, and both autosomal dominant and autosomal recessive (AR) inheritance have been reported, but no genes have been identified or localized for nonsyndromic SD in humans. We performed genomewide scanning by homozygosity mapping in a large consanguineous ARSD Arab Israeli family with six definitely affected members. Significant linkage was found to chromosome 19q13, with a LOD score of 6.9. This was confirmed in a second Pakistani family with three affected members, with a LOD score of 2.4. The combined-haplotype data identify a critical region between D19S570 and D19S908, an interval of 8.5 cM on 19q13.1-19q13.3. This is the first study to localize a gene for nonsyndromic SD. ARSD is clinically heterogeneous and is likely to result from mutations in developmental genes or from regulating transcription factors. Identification of these genes will improve the understanding of the molecular processes contributing to both normal and abnormal human vertebral development.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Turnpenny PD,Bulman MP,Frayling TM,Abu-Nasra TK,Garrett C,Hattersley AT,Ellard Sdoi
10.1086/302464subject
Has Abstractpub_date
1999-07-01 00:00:00pages
175-82issue
1eissn
0002-9297issn
1537-6605pii
S0002-9297(07)63741-0journal_volume
65pub_type
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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