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.
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: Ingrid C Rulifson; Patrick Collins; Li Miao; Dana Nojima; Ki Jeong Lee; Miki Hardy; Jamila Gupte; Kelly Hensley; Kim Samayoa; Cynthia Cam; James B Rottman; Mike Ollmann; William G Richards; Yang Li Journal: J Biol Chem Date: 2016-12-23 Impact factor: 5.157
Authors: Tobias Laurell; Daniel Nilsson; Wolfgang Hofmeister; Anna Lindstrand; Nadav Ahituv; Julia Vandermeer; Anders Amilon; Göran Annerén; Marianne Arner; Maria Pettersson; Nina Jäntti; Hans-Eric Rosberg; Peter A Cattini; Agneta Nordenskjöld; Outi Mäkitie; Giedre Grigelioniene; Ann Nordgren Journal: Mol Genet Genomic Med Date: 2014-05-14 Impact factor: 2.183
Authors: Taru Tukiainen; Matti Pirinen; Antti-Pekka Sarin; Claes Ladenvall; Johannes Kettunen; Terho Lehtimäki; Marja-Liisa Lokki; Markus Perola; Juha Sinisalo; Efthymia Vlachopoulou; Johan G Eriksson; Leif Groop; Antti Jula; Marjo-Riitta Järvelin; Olli T Raitakari; Veikko Salomaa; Samuli Ripatti Journal: PLoS Genet Date: 2014-02-06 Impact factor: 5.917