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J Med Genet. 2013 Dec;50(12):802-11. doi: 10.1136/jmedgenet-2013-101644. Epub 2013 Oct 11.

Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing.

Author information

1
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

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 AND RESULTS:

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.

KEYWORDS:

Genetics

PMID:
24123876
DOI:
10.1136/jmedgenet-2013-101644
[Indexed for MEDLINE]
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