Abstract
Non-syndromic intellectual disability (NSID) is mental retardation in persons of normal physical appearance who have no recognisable features apart from obvious deficits in intellectual functioning and adaptive ability; however, its genetic etiology of most patients has remained unknown. The main purpose of this study was to fine map and identify specific causal gene(s) by genotyping a NSID family cohort using a panel of markers encompassing a target region reported in a previous work. A total of 139 families including probands, parents and relatives were included in the household survey, clinical examinations and intelligence tests, recruited from the Qinba mountain region of Shannxi province, western China. A collection of 34 tagged single nucleotide polymorphisms (tSNPs) spanning five microsatellite marker (STR) loci were genotyped using an iPLEX Gold assay. The association between tSNPs and patients was analyzed by family-based association testing (FBAT) and haplotype analysis (HBAT). Four markers (rs5974392, rs12164331, rs5929554 and rs3116911) in a block that showed strong linkage disequilibrium within the first three introns of the LOC 101928437 locus were found to be significantly associated with NSID (all P<0.01) by the FBAT method for a single marker in additive, dominant and recessive models. The results of haplotype tests of this block also revealed a significant association with NSID (all P<0.05) using 2-window and larger HBAT analyses. These results suggest that LOC 101928437 is a novel candidate gene for NSID in Han Chinese individuals of the Qinba region of China. Although the biological function of the gene has not been well studied, knowledge about this gene will provide insights that will increase our understanding of NSID development.
Highlights
Intellectual disability (ID), known as mental retardation, has a 2% prevalence in the population [1]
Three blocks with high linkage disequilibrium (LD) distribution were found in our samples, which was in line with the result of LD distribution analysis with HapMap data set
We sought to clarify the associations among five spanning five microsatellite marker (STR) markers located on the X chromosome and conduct fine mapping using independent family cohort samples
Summary
Intellectual disability (ID), known as mental retardation, has a 2% prevalence in the population [1]. ID is a common disorder involving significantly lower intellectual function and lower social adaptive ability prior to the age of 18 years. 30% of individuals with mild ID do not have other obvious clinical syndromes; they are defined as having non-syndromic intellectual disability (NSID) [2]. 25% of all cases of ID are caused by a genetic disorder, typically, the etiology of this disability is poorly understood. Strong evidence from numerous carefully performed studies has suggested that genetic factor is an important causative etiology of NSID which are present in 25–50% of ID patients, and this number increases proportionally with severity [3]. As more NSID genes are identified, more of the common biological pathways that are involved in NSID will be uncovered, which will help us to understand, prevent and alleviate this disorder
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