Inheritance of polyalanine expansion mutation of PHOX2B in congenital central hypoventilation syndrome.
J Hum Genet
; 57(5): 335-7, 2012 May.
Article
em En
| MEDLINE
| ID: mdl-22437207
ABSTRACT
Congenital central hypoventilation syndrome (CCHS; MIM 209880) is caused mostly by dominant alanine expansion (most prevalent is 7-alanine expansion) mutations in PHOX2B. More than 90% of the alanine expansion mutations had been considered to be de novo due to unequal crossover during gametogenesis. However, a recent report stated that 25% of patients inherited the alanine-expanded allele from their parents with somatic mosaicism or constitutive mutation. We studied inheritance in 45 unrelated families, and found that one patient (2%) inherited 5-alanine expansion mutation from a parent with late-onset central hypoventilation syndrome and nine patients (20%) inherited 5- to 7-alanine expansion mutation from apparently asymptomatic parents with somatic mosaicism. Analysis using a sensitive method would be recommended to all parents of CCHS proband due to high incidence of somatic mosaicism. The absence of an alanine-contracted allele (expected counterpart allele in unequal crossover) and the highest prevalence of 6-alanine expansion mutation in somatic mosaicism suggest that the somatic mosaicism is likely caused by a mechanism other than an unequal crossover, such as a replication mechanism.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Proteínas de Homeodomínio
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Apneia do Sono Tipo Central
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Hipoventilação
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Mosaicismo
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Mutação
Tipo de estudo:
Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article