Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing.
J Med Genet
; 50(12): 802-11, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-24123876
ABSTRACT
BACKGROUND:
Intellectual disability (ID) is a common neurodevelopmental disorder affecting 1-3% of the general population. Mutations in more than 10% of all human genes are considered to be involved in this disorder, although the majority of these genes are still unknown.OBJECTIVES:
We investigated 19 small non-consanguineous families with two to five affected siblings in order to identify pathogenic gene variants in known, novel and potential ID candidate genes. Non-consanguineous families have been largely ignored in gene identification studies as small family size precludes prior mapping of the genetic defect. METHODS ANDRESULTS:
Using exome sequencing, we identified pathogenic mutations in three genes, DDHD2, SLC6A8, and SLC9A6, of which the latter two have previously been implicated in X-linked ID phenotypes. In addition, we identified potentially pathogenic mutations in BCORL1 on the X-chromosome and in MCM3AP, PTPRT, SYNE1, and ZNF528 on autosomes.CONCLUSIONS:
We show that potentially pathogenic gene variants can be identified in small, non-consanguineous families with as few as two affected siblings, thus emphasising their value in the identification of syndromic and non-syndromic ID genes.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Exoma
/
Deficiência Intelectual
/
Mutação
Tipo de estudo:
Diagnostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Med Genet
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Holanda