A gene for autosomal recessive spondylocostal dysostosis maps to 19q13.1-q13.3

In spondylocostal dysostosis (SD), vertebral-segmentation defects are assoc iated with rib anomalies. This results in short-trunk short stature, nonpro gressive kyphoscoliosis, and radiological features of multiple hemivertebra e and rib fusions. SD can be familial, and both autosomal dominant and auto somal recessive (AR) inheritance have been reported, but no genes have been identified or localized for nonsyndromic SD in humans. Vile performed geno mewide scanning by homozygosity mapping in a large consanguineous ARSD Arab Israeli family with six definitely affected members. Significant linkage w as found to chromosome 19q13, with a LOD score of 6.9. This was confirmed i n a second Pakistani family with three affected members, with a LOD score o f 2.4. The combined-haplotype data identify a critical region between D19S5 70 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 heterogen eous and is likely to result from mutations in developmental genes or from regulating transcription factors. Identification of these genes will improv e the understanding of the molecular processes contributing to both normal and abnormal human vertebral development.