[Genetic analysis of a Chinese pedigree with congenital synpolydactyly]

Syndactyly is a limb malformation that shows a characteristic manifestation in both hands and feet. This condition is inherited as an autosomal dominant trait with reduced penetrance. Clinical presentation, in general, is complete or partial webbing between 3rd and 4th fingers. Syndactyly type I, II and III were mapped to 2q34-36, 2q31-q32 and 6q21-23.2 respectively. Syndactyly type II is named as synpolydactyly (SPD). Expansion of a polyalanine tract in the HOXD13 gene is known to cause synpolydactyly. HOXD13 gene locates in the HoxD complex. Nine homologous genes (HOXD1, -D3, -D4, -D8, -D9, -D10, -D11, -D12, -D13) of HoxD complex locate on chromosome 2 in the order of HOXD1 to HOXD13, among which HOXD13 is closest to the centromere. Deletions and duplications in HoxD complex or its upstream regulator factors have been identified to cause hand heteroplasia and consequently lead to abnormity of finger number or abnormity of configuration. We performed linkage analysis in a kindred with autosomal dominant hereditary syndactyly. Tight linkage to markers on chromosome 2q31-q32 (maximum two-point lod score: 6.78 at recombination fraction theta = 0.00) was observed. Multipoint linkage analysis produced a maximum LOD score of 7.02. Haplotype construction and analysis of recombination events narrowed this locus to a 20.61 cM region between markers D2S2302 and D2S315. No mutation was found in the coding region, the intro-exon boundaries, or part of the promoter region of HOXD13. Our result demonstrates that synpolydactyly locus in the Chinese Han Population is in the region of chromosome 2q31-q32 but a different causal gene can be involved.