A novel insertion and deletion mutation in the BHLHA9 underlies polydactyly and mesoaxial synostotic syndactyly with phalangeal reduction

Abstract Mesoaxial syndactylyis characterized by fusion of the central digits. The disorder segregates in autosomalrecessive pattern and mapped on human chromosome 17p13.3. Homozygous missense mutationsin the BHLHA9 have been reported to cause mesoaxial synostotic syndactylywith phalangealreduction (MSSD). In the present study, we have investigated a family segregating mesoaxial synostotic syndactylywith phalangealreduction (MSSD) in autosomalrecessive manner. Genotyping using microsatellite markers followed by Sanger sequencingrevealed a homozygous deletion and insertion mutation (NM_001164405: c.252_270delinsGCA; p.(Phe85Glufs*108)) in the BHLHA9 gene in affected individuals of the family. This study reports the first frameshift mutationin the BHLHA9 causing mesoaxial synostotic syndactylyand phalangealreduction.