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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 ; Pettersson, Maria ; Jäntti, Nina ; Rosberg, Hans‐Eric ; Cattini, Peter A ; Nordenskjöld, Agneta ; Mäkitie, Outi ; Grigelioniene, Giedre ; Nordgren, Ann

Molecular genetics & genomic medicine, 2014-09, Vol.2 (5), p.402-411 [Peer Reviewed Journal]

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  • Title:
    Identification of three novel FGF16 mutations in X‐linked recessive fusion of the fourth and fifth metacarpals and possible correlation with heart disease
  • Author: Laurell, Tobias ; Nilsson, Daniel ; Hofmeister, Wolfgang ; Lindstrand, Anna ; Ahituv, Nadav ; Vandermeer, Julia ; Amilon, Anders ; Annerén, Göran ; Arner, Marianne ; Pettersson, Maria ; Jäntti, Nina ; Rosberg, Hans‐Eric ; Cattini, Peter A ; Nordenskjöld, Agneta ; Mäkitie, Outi ; Grigelioniene, Giedre ; Nordgren, Ann
  • Subjects: FGF16 ; MF4 ; metacarpal fusion ; heart ; Original ; Medicinsk genetik ; Basic Medicine ; Medical Genetics ; Medical and Health Sciences ; Medicin och hälsovetenskap ; Medicinska och farmaceutiska grundvetenskaper
  • Is Part Of: Molecular genetics & genomic medicine, 2014-09, Vol.2 (5), p.402-411
  • Description: 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. 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 the identified FGF16 changes were confirmed using mutated human FGF16 message and 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.
  • Publisher: United States: Blackwell Publishing Ltd
  • Language: English
  • Identifier: ISSN: 2324-9269
    EISSN: 2324-9269
    DOI: 10.1002/mgg3.81
    PMID: 25333065
  • Source: © ProQuest LLC All rights reserved

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