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Identification of three novel FGF16 mutations in X-linked recessive fusion of the fourth and fifth metacarpals and possible correlation with heart disease.

Laurell, Tobias; Nilsson, Daniel; Hofmeister, Wolfgang; Lindstrand, Anna; Ahituv, Nadav; Vandermeer, Julia; Amilon, Anders; Annerén, Göran; Arner, Marianne and Pettersson, Maria, et al. (2014) In Molecular Genetics & Genomic Medicine 2(5). p.402-411
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... (More)
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. (Less)
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Molecular Genetics & Genomic Medicine
volume
2
issue
5
pages
402 - 411
publisher
John Wiley & Sons
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  • pmid:25333065
ISSN
2324-9269
DOI
10.1002/mgg3.81
language
English
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yes
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8dc06c2a-f5c7-44fc-8778-d13684fd718a (old id 4733663)
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http://www.ncbi.nlm.nih.gov/pubmed/25333065?dopt=Abstract
date added to LUP
2014-11-10 00:03:39
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2016-09-20 04:10:56
@article{8dc06c2a-f5c7-44fc-8778-d13684fd718a,
  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.},
  author       = {Laurell, Tobias and Nilsson, Daniel and Hofmeister, Wolfgang and Lindstrand, Anna and Ahituv, Nadav and Vandermeer, Julia and Amilon, Anders and Annerén, Göran and Arner, Marianne and Pettersson, Maria and Jäntti, Nina and Rosberg, HansE and Cattini, Peter A and Nordenskjöld, Agneta and Mäkitie, Outi and Grigelioniene, Giedre and Nordgren, Ann},
  issn         = {2324-9269},
  language     = {eng},
  number       = {5},
  pages        = {402--411},
  publisher    = {John Wiley & Sons},
  series       = {Molecular Genetics & Genomic Medicine},
  title        = {Identification of three novel FGF16 mutations in X-linked recessive fusion of the fourth and fifth metacarpals and possible correlation with heart disease.},
  url          = {http://dx.doi.org/10.1002/mgg3.81},
  volume       = {2},
  year         = {2014},
}