Open AccessIdentification of three novel FGF16 mutations in X‐linked recessive fusion of the fourth and fifth metacarpals and possible correlation with heart disease
Author(s) -
Laurell Tobias,
Nilsson Daniel,
Hofmeister Wolfgang,
Lindstrand Anna,
Ahituv Nadav,
Vandermeer Julia,
Amilon Anders,
Annerén Göran,
Arner Marianne,
Pettersson Maria,
Jäntti Nina,
Rosberg HansEric,
Cattini Peter A.,
Nordenskjöld Agneta,
Mäkitie Outi,
Grigelioniene Giedre,
Nordgren Ann
Publication year - 2014
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.81
Subject(s) - genetics , penetrance , phenotype , biology , exome sequencing , nonsense mutation , exon , mutation , disease , x linked recessive inheritance , zebrafish , clinical phenotype , medicine , missense mutation , gene , x chromosome
Nonsense mutations in FGF 16 have recently been linked to X‐linked recessive hand malformations with fusion between the fourth and the fifth metacarpals and hypoplasia of the fifth digit ( MF 4; MIM#309630). The purpose of this study was to perform careful clinical phenotyping and to define molecular mechanisms behind X‐linked recessive MF 4 in three unrelated families. We performed whole‐exome sequencing, and identified three novel mutations in FGF 16 . The functional impact of FGF 16 loss was further studied using morpholino‐based suppression of fgf16 in zebrafish. In addition, clinical investigations revealed reduced penetrance and variable expressivity of the MF 4 phenotype. Cardiac disorders, including myocardial infarction and atrial fibrillation followed the X‐linked FGF 16 mutated trait in one large family. Our findings establish that a mutation in exon 1, 2 or 3 of FGF 16 results in X‐linked recessive MF 4 and expand the phenotypic spectrum of FGF 16 mutations to include a possible correlation with heart disease.