Identical mutations in NOG can cause either tarsal/carpal coalition syndrome or proximal symphalangism

Purpose: To identify the gene causing tarsal/carpal coalition syndrome (TCC).

Methods: Individuals from three kindreds with TCC and normal hearing were used to map TCC and screen for mutations in Noggin (NOG).

Results: Three different missense mutations in NOG were found. Two of these mutations are identical to mutations previously reported to cause proximal symphalangism (SYM1).

Conclusions: TCC is allelic to SYM1, and at least two different mutations in NOG can result in either TCC or SYM1 in different families. This finding suggests that phenotypic differences between these conditions are caused by epistatic modifiers of NOG.