Mild brachydactyly type A1 maps to chromosome 2q35-q36 and is caused by a novel IHH mutation in a three generation family

Abstract

The brachydactylies are a group of inherited disorders in which different subtypes have been defined on the basis of the specific pattern of digital bones involved. Recently, mutations in the Indian hedgehog (IHH) gene on chromosome 2q2q35-q36 have been shown to cause BDA-1 in three large families from China. However, several phenotypes and locus heterogeneity have been described for BDA-1, with an additional locus mapped on chromosome 5p13.3-p13.2. We describe a three generation family of Italian descent affected by mild BDA-1, without any additional clinical abnormality except for short stature. Linkage analysis showed segregation compatible with a locus at 2q35-q36 and mutation screening of the IHH gene showed the presence of a heterozygous c.298G>A transition in exon 1, resulting in the substitution of asparagine for aspartic acid at residue 100. This paper confirms IHH as a major gene responsible for BDA-1