Germline mutation in DOK7 associated with fetal akinesia deformation sequence.
J Med Genet
; 46(5): 338-40, 2009 May.
Article
em En
| MEDLINE
| ID: mdl-19261599
ABSTRACT
BACKGROUND:
Fetal akinesia deformation sequence syndrome (FADS) is a heterogeneous disorder characterised by fetal akinesia and developmental defects including, in some case, pterygia. Multiple pterygium syndromes (MPS) are traditionally divided into prenatally lethal and non-lethal (such as Escobar) types. Previously, we and others reported that homozygous mutations in the fetal acetylcholine receptor gamma subunit (CHRNG) can cause both lethal and non-lethal MPS, demonstrating that pterygia resulted from fetal akinesia, and that mutations in the acetylcholine receptor subunits CHRNA1, CHRND, and Rapsyn (RAPSN) can also result in a MPS/FADS phenotype.METHODS:
We hypothesised that mutations in other acetylcholine receptor related genes may interfere with neurotransmission at the neuromuscular junction and so we analysed 14 cases of lethal MPS/FADS without CHRNG, CHRNA1, CHRNB1, CHRND, or RAPSN mutations for mutations in DOK7.RESULTS:
A homozygous DOK7 splice site mutation, c.331+1G>T, was identified in a family with three children affected with lethal FADS. Previously DOK7 mutations have been reported to underlie a congenital myaesthenic syndrome with a characteristic "limb girdle" pattern of muscle weakness.CONCLUSION:
This finding is consistent with the hypothesis that whereas incomplete loss of DOK7 function may cause congenital myasthenia, more severe loss of function can result in a lethal fetal akinesia phenotype.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anormalidades Múltiplas
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Mutação em Linhagem Germinativa
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Proteínas Musculares
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Child
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Female
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Humans
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Male
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article