title: Whole exome sequencing identifies FGF16 nonsense mutations as the cause of X-linked recessive metacarpal 4/5 fusion.
abstract: 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.
authors.affiliation: Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland. jamsheer@wp.pl
authors.forename: Aleksander
authors.initials: A
authors.lastname: Jamsheer
authors.forename: Tomasz
authors.initials: T
authors.lastname: Zemojtel
authors.forename: Mateusz
authors.initials: M
authors.lastname: Kolanczyk
authors.forename: Sigmar
authors.initials: S
authors.lastname: Stricker
authors.forename: Jochen
authors.initials: J
authors.lastname: Hecht
authors.forename: Peter
authors.initials: P
authors.lastname: Krawitz
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Doelken
authors.forename: Renata
authors.initials: R
authors.lastname: Glazar
authors.forename: Magdalena
authors.initials: M
authors.lastname: Socha
authors.forename: Stefan
authors.initials: S
authors.lastname: Mundlos
mesh_terms: D002648:Child; D018389:Codon, Nonsense; D004622:Embryo, Mammalian; D059472:Exome; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006228:Hand Deformities, Congenital / Q000235:genetics*; D006801:Humans; D008297:Male; D050279:Metacarpal Bones / Q000002:abnormalities*; D009928:Organ Specificity; D017422:Sequence Analysis, DNA
chemical_list: D018389:Codon, Nonsense; C512705:FGF16 protein, human; D005346:Fibroblast Growth Factors
keywords: FGF16; X-linked inheritance; metacarpal 4-5 fusion; metacarpal synostosis; nonsense mutation