Brachydactyly: molecular bases and phenotypic variability.
The term brachydactyly indicates shortening of the hands and/or feet digits due to lack or abnormal development of phalanges, metacarpals or both. It may occur as an isolated trait or as part of a syndrome. According to the skeletal involvement, the isolated brachydactyly forms are categorized in the groups A-E, including several subgroups. However, there is a considerable phenotypic overlap. The isolated forms usually occur as autosomal dominant traits and show variable expressivity and incomplete penetrance; they are often caused by mutation in various components of the BMP pathway and its modulators.
We plan to investigate molecular bases of brachydactyly, studying a three-generation pedigree in which the proband is affected by an isolated form of brachydactyly with features of type A1 and type C, as his maternal grandfather; his mother shows a very mild phenotype. Whole exome sequencing (WES) will be performed on the proband and his grandfather and candidate variants will be selected to be validated through Sanger sequencing.