PT - JOURNAL ARTICLE AU - Aleksander Jamsheer AU - Tomasz Zemojtel AU - Mateusz Kolanczyk AU - Sigmar Stricker AU - Jochen Hecht AU - Peter Krawitz AU - Sandra C Doelken AU - Renata Glazar AU - Magdalena Socha AU - Stefan Mundlos TI - Whole exome sequencing identifies <em>FGF16</em> nonsense mutations as the cause of X-linked recessive metacarpal 4/5 fusion AID - 10.1136/jmedgenet-2013-101659 DP - 2013 May 23 TA - Journal of Medical Genetics PG - jmedgenet-2013-101659 4099 - http://jmg.bmj.com/content/early/2013/05/23/jmedgenet-2013-101659.short 4100 - http://jmg.bmj.com/content/early/2013/05/23/jmedgenet-2013-101659.full AB - 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.