FMR1 allele size distribution in 35,000 males and females: a comparison of developmental delay and general population cohorts.
Genet Med
; 20(12): 1627-1634, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-29595813
ABSTRACT
PURPOSE:
Developmental delay phenotypes have been associated with FMR1 premutation (PM 55-200 CGG repeats) and "gray zone" (GZ 45-54 CGG repeats) alleles. However, these associations have not been confirmed by larger studies to be useful in pediatric diagnostic or screening settings.METHODS:
This study determined the prevalence of PM and GZ alleles in two independent cohorts of 19,076 pediatric referrals to developmental delay diagnostic testing through Victorian Clinical Genetics Service (cohort 1 N = 10,235; cohort 2 N = 8841), compared with two independent general population cohorts (newborn screening N = 1997; carrier screening by the Victorian Clinical Genetics Service prepair program N = 14,249).RESULTS:
PM and GZ prevalence rates were not significantly increased (p > 0.05) in either developmental delay cohort (male PM 0.12-0.22%; female PM 0.26-0.33%; male GZ 0.68-0.69%; female GZ 1.59-2.13-%) compared with general population cohorts (male PM 0.20%; female PM 0.27-0.82%; male GZ 0.79%; female GZ 1.43-2.51%). Furthermore, CGG size distributions were comparable across datasets, with each having a modal value of 29 or 30 and ~1/3 females and ~1/5 males having at least one allele with ≤26 CGG repeats.CONCLUSION:
These data do not support the causative link between PM and GZ expansions and developmental-delay phenotypes in pediatric settings.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Deficiências do Desenvolvimento
/
Expansão das Repetições de Trinucleotídeos
/
Proteína do X Frágil da Deficiência Intelectual
/
Síndrome do Cromossomo X Frágil
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
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Child
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Child, preschool
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Female
/
Humans
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Infant
/
Male
/
Newborn
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article