Universität zu Köln

Kakar, Naseebullah, Goebel, Ingrid, Daud, Shakeela, Nuernberg, Gudrun, Agha, Noor, Ahmad, Adeel, Nuernberg, Peter, Kubisch, Christian ORCID: 0000-0003-4220-0978, Ahmad, Jamil and Borck, Guntram (2012). A homozygous splice site mutation in TRAPPC9 causes intellectual disability and microcephaly. Eur. J. Med. Genet., 55 (12). S. 727 - 732. AMSTERDAM: ELSEVIER. ISSN 1878-0849

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Abstract

Autosomal recessive intellectual disability is believed to be particularly prevalent in highly consanguineous populations and genetic isolates and may account for a quarter of all non-syndromic cases. Mutations in more than 50 genes have been reported to be involved in autosomal recessive intellectual disability, including TRAPPC9 (MIM 611966), mutations of which have been identified in six families from different geographical origins. We performed a clinical and molecular genetic study of a consanguineous Pakistani family segregating intellectual disability and microcephaly. SNP-array-based homozygosity mapping revealed suggestive linkage to four genomic regions including one on chromosome 8 that contained TRAPPC9. We detected a homozygous TRAPPC9 splice donor site mutation (c.1024+1G>T) that cosegregated with intellectual disability in the family and led to skipping of exon 3 and exons 3 and 4 in blood-derived patient RNA. We have thus identified a novel splice site mutation leading to exon skipping and premature termination of TRAPPC9 translation. These data further suggest that TRAPPC9 mutations -unlike mutations in the vast majority of the known intellectual disability-associated genese- constitute a more frequent cause of autosomal-recessive cognitive deficits, especially when microcephaly is also present. (C) 2012 Elsevier Masson SAS. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kakar, Naseebullah UNSPECIFIED UNSPECIFIED UNSPECIFIED Goebel, Ingrid UNSPECIFIED UNSPECIFIED UNSPECIFIED Daud, Shakeela UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Gudrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Agha, Noor UNSPECIFIED UNSPECIFIED UNSPECIFIED Ahmad, Adeel UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Kubisch, Christian UNSPECIFIED orcid.org/0000-0003-4220-0978 UNSPECIFIED Ahmad, Jamil UNSPECIFIED UNSPECIFIED UNSPECIFIED Borck, Guntram UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-477939
DOI:	10.1016/j.ejmg.2012.08.010
Journal or Publication Title:	Eur. J. Med. Genet.
Volume:	55
Number:	12
Page Range:	S. 727 - 732
Date:	2012
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1878-0849
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BETA-BINDING PROTEIN; MENTAL-RETARDATION; PREVALENCE; NIK Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47793