Publication
Title
3p25.3 microdeletion of GABA transporters SLC6A1 and SLC6A11 results in intellectual disability, epilepsy and stereotypic behavior
Author
Abstract
Small interstitial deletions affecting chromosome region 3p25.3 have been reported in only five patients so far, four of them with overlapping telomeric microdeletions 3p25.3 and variable features of 3p- syndrome, and one patient with a small proximal microdeletion and a distinct phenotype with intellectual disability (ID) and multiple congenital anomalies. Here we report on three novel patients with overlapping proximal microdeletions 3p25.3 of 1.1-1.5Mb in size showing a consistent non-3p- phenotype with ID, epilepsy/EEG abnormalities, poor speech, ataxia and stereotypic hand movements. The smallest region of overlap contains two genes encoding sodium- and chloride-dependent GABA transporters which have not been associated with this disease phenotype in humans so far. The protein function, the phenotype in transporter deficient animal models and the effects of specific pharmacological transporter inhibition in mice and humans provide evidence that these GABA transporters are plausible candidates for seizures/EEG abnormalities, ataxia and ID in this novel group of patients. A fourth novel patient deleted for a 3.16Mb region, both telomeric and centromeric to 3p25.3, confirms that the telomeric segment is critical for the 3p- syndrome phenotype. Finally, a region of 643kb is suggested to harbor one or more genes causative for polydactyly which is part of the 3p- syndrome. (c) 2014 Wiley Periodicals, Inc.
Language
English
Source (journal)
American journal of medical genetics : part A. - Bognor Regis, 2003, currens
Publication
Bognor Regis : 2014
ISSN
1552-4825 [print]
1552-4833 [online]
Volume/pages
164A:12(2014), p. 3061-3068
ISI
000345293300014
Full text (Publishers DOI)
Full text (publishers version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 13.01.2015
Last edited 20.04.2017
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