Abstract
BackgroundIntellectual disability (ID) is a serious disorder of the central nervous system with a prevalence of 1-3% in a general population. In the past decades, the research focus has been predominantly on X-linked ID (68 loci and 19 genes for non syndromic X linked ID) while for autosomal recessive nonsyndromic ID (NSID) only 30 loci and 6 genes have been reported to date.MethodsGenome-wide homozygosity mapping with 500 K Nsp1 array (Affymetrix), CNV analysis, PCR based breakpoint mapping and DNA sequencing was performed to explore the genetic basis of autosomal recessive nonsyndromic ID in a large Pakistani family.ResultsData analysis showed linkage at 8p23 locus with common homozygous region between SNPs rs6989820 and rs2237834, spanning a region of 12.494 Mb. The subsequent CNV analysis of the data revealed a homozygous deletion of 170.673 Kb which encompassed the TUSC3 gene.ConclusionWe report a novel deletion mutation in TUSC3 gene which is the second gene after TRAPPC9 in which mutation has been identified in more than one family with autosomal recessive NSID. The study will aid in exploring the molecular pathway of cognition.
Highlights
Intellectual disability (ID) is a serious disorder of the central nervous system with a prevalence of 13% in a general population
To date 30 loci including six known genes have been reported to be involved in autosomal recessive NS-ID (ARNS-ID) [4]
In this study we present the clinical and molecular analysis of a consanguineous Pakistani family with autosomal recessive NS-ID, and report a novel mutation comprising deletion of the entire TUSC3 gene and its down stream region at the 8p23 locus
Summary
Intellectual disability (ID) is a serious disorder of the central nervous system with a prevalence of 13% in a general population. To date 30 loci including six known genes have been reported to be involved in autosomal recessive NS-ID (ARNS-ID) [4]. Its p arm showed high degree of sequence variations, within its distal-most ~15 megabase region This region is believed to be of prime importance in the human genome because of the high expression pattern of nervous system related genes, and has recently been touted as a “hub” for neuropsychiatric developmental disorders [15]. One gene for microcephaly (MCPH1) and one gene for NS-ID, namely TUSC3, have been identified on 8p
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
