RT Journal Article SR Electronic T1 Whole exome sequencing identifies FGF16 nonsense mutations as the cause of X-linked recessive metacarpal 4/5 fusion JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP jmedgenet-2013-101659 DO 10.1136/jmedgenet-2013-101659 A1 Aleksander Jamsheer A1 Tomasz Zemojtel A1 Mateusz Kolanczyk A1 Sigmar Stricker A1 Jochen Hecht A1 Peter Krawitz A1 Sandra C Doelken A1 Renata Glazar A1 Magdalena Socha A1 Stefan Mundlos YR 2013 UL http://jmg.bmj.com/content/early/2013/05/23/jmedgenet-2013-101659.abstract 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.