Further evidence for FGF16 truncating mutations as the cause of X-linked recessive fusion of metacarpals 4 / 5.
Birth Defects Res A Clin Mol Teratol
; 100(4): 314-8, 2014 Apr.
Article
em En
| MEDLINE
| ID: mdl-24706454
ABSTRACT
BACKGROUND:
Metacarpal 4-5 fusion (MF4; MIM#309630) is a rare congenital malformation of the hand characterized 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. Recently, we have identified FGF16 nonsense mutations as the underlying cause of isolated X-linked recessive MF4.METHODS:
In this report, we provide a detailed clinical description of a sporadic male patient showing MF4 in whom we performed Sanger sequencing of the entire coding sequence of FGF16.RESULTS:
In addition to MF4 symptoms, the patient presented with generalized joint laxity and hypermobility. FGF16 sequencing detected a novel truncating mutation (c.474_477del; p.E158DfsX25) in exon 3 of the gene. A heterozygous mutation was found in a clinically and radiologically unaffected mother of the proband.CONCLUSION:
Our finding confirms that truncating mutations of FGF16 are causative for X-linked recessive metacarpal 4-5 fusion. Importantly, the mutation detected in this study was located in last exon of the gene (exon 3), like the only two FGF16 disease-causing variants identified to date. Thus, all FGF16 mutations known to give rise to this rare skeletal hand malformation are C-terminal and most probably do not result in a nonsense mediated decay. Additionally, our proband showed mild symptoms of a connective tissue disorder, as some other patients previously reported to have X-linked MF4. Therefore, we suggest that impaired FGF16 function may also be responsible for connective tissue symptoms in MF4 patients.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Deformidades Congênitas da Mão
/
Doenças Genéticas Ligadas ao Cromossomo X
/
Ossos Metacarpais
/
Genes Ligados ao Cromossomo X
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Mutação INDEL
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Fatores de Crescimento de Fibroblastos
/
Genes Recessivos
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article