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

Eur J Med Genet. 2019 Apr;62(4):278-281. doi: 10.1016/j.ejmg.2018.08.005. Epub 2018 Aug 11.

Abstract

Mesoaxial syndactyly is characterized by fusion of the central digits. The disorder segregates in autosomal recessive pattern and mapped on human chromosome 17p13.3. Homozygous missense mutations in the BHLHA9 have been reported to cause mesoaxial synostotic syndactyly with phalangeal reduction (MSSD). In the present study, we have investigated a family segregating mesoaxial synostotic syndactyly with phalangeal reduction (MSSD) in autosomal recessive manner. Genotyping using microsatellite markers followed by Sanger sequencing revealed 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 mutation in the BHLHA9 causing mesoaxial synostotic syndactyly and phalangeal reduction.

Keywords: BHLHA9; Indel variant; Mesoaxial synostotic syndactyly; Phalangeal reduction.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Child
  • Female
  • Fingers / abnormalities*
  • Fingers / pathology
  • Frameshift Mutation
  • Humans
  • INDEL Mutation*
  • Male
  • Pedigree
  • Polydactyly / genetics*
  • Polydactyly / pathology
  • Syndactyly / genetics*
  • Syndactyly / pathology
  • Toes / abnormalities*
  • Toes / pathology

Substances

  • BHLHA9 protein, human
  • Basic Helix-Loop-Helix Transcription Factors

Supplementary concepts

  • Syndactyly, Mesoaxial Synostotic, with Phalangeal Reduction