Whole exome sequencing identifies FGF16 nonsense mutations as the cause of X-linked recessive metacarpal 4/5 fusion
- J Med Genet. 2013 Sep;50(9):579-84. doi: 10.1136/jmedgenet-2013-101659.
- 1. Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland. [email protected]
Background: Metacarpal 4-5 fusion (MF4; MIM %309630) is a rare congenital malformation of the hand characterised by the partial or complete fusion of the fourth and fifth metacarpals. The anomaly occurs as an isolated trait or part of a genetic syndrome.
Methods: To search for disease-causing mutation, whole exome Sequencing (WES) was performed on samples from a single Trio. Before WES, molecular screening including gene Sequencing and array comparative genomic hybridisation was applied. Validation of WES and segregation studies were done using routine Sanger Sequencing.
Results: Exome Sequencing detected a nonsense mutation (c.C535T; p.R179X) in exon 3 of the FGF16 gene, which maps to chromosome Xq21.1. Mutational screening of the FGF16 gene performed in an unrelated proband of different ethnicity showed another nonsense mutation in exon 3 (c.C470A; p.S157X).
Conclusions: This study shows that truncating mutations of FGF16 are associated with X-linked recessive metacarpal 4-5 fusion. The study provides evidence for the involvement of FGF16 in the fine tuning of the human skeleton of the hand.