Identification of three novelFGF16mutations in X‐linked recessive fusion of the fourth and fifth metacarpals and possible correlation with heart disease
Year: 2014
Type: article
Abstract: Nonsense mutations in FGF16 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 (MF4; MIM#309630). The purpose of this study was to perform careful clinical phenotyping and to define molecular mechanisms behind X-linked recessive MF4 in three unrelated families. We performed whole-exome sequencing, and identified three novel mutations in FGF16. The functional impact of FGF16 loss was further studied using morpholino-based suppression of fgf16 in zebrafish. In addition, clinical investigations revealed reduced penetrance and variable expressivity of the MF4 phenotype. Cardiac disorders, including myocardial infarction and atrial fibrillation followed the X-linked FGF16 mutated trait in one large family. Our findings establish that a mutation in exon 1, 2 or 3 of FGF16 results in X-linked recessive MF4 and expand the phenotypic spectrum of FGF16 mutations to include a possible correlation with heart disease.
DOI: 10.1002/mgg3.81
Institutions: Karolinska Institutet, Stockholm South General Hospital, Karolinska University Hospital, Science for Life Laboratory, University of California, San Francisco, Örebro University Hospital, Uppsala University, Lund University, Skåne University Hospital, University of Manitoba, Folkhälsans Forskningscentrum
Language: English
Subfield: Developmental Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,900
Funders: Folkhälsanin Tutkimussäätiö, Kommunfullmäktige, Stockholms Stad, Karolinska Institutet, Vetenskapsrådet, Stiftelsen Samariten, Sällskapet Barnavård, Uppsala Multidisciplinary Center for Advanced Computational Science, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
OpenAlex ID: W2029814079