"Familial" versus "Sporadic" intellectual disability: contribution of common microdeletion and microduplication syndromes

Abstract

BackgroundInterstitial Microdeletion and Microduplication syndromes have been proposed as a significant cause of sporadic intellectual disability (ID) but the role of such aberrations in familial ID has not yet been investigated. As the balanced chromosomal abnormalities commonly lead to the recurrent ID or multiple congenital anomalies, this study was designed to evaluate whether it was justified to investigate such aberrations in familial ID patients. Three hundred and twenty eight patients from 101 unrelated Iranian families with more than two ID patients in the first-degree relatives, have been investigated. Assessment of a panel of 21 common Microdeletion and Microduplication syndromes (CMMS) was carried out using Multiplex Ligation-Dependent Probe Amplification (MLPA) technique.ResultsAmong the families studied, 27.7% had 4-12, 35.6% had 3 and 36.6% had 2 affected individuals in the first-degree relatives. An autosomal dominant inheritance of Williams-Beuren syndrome (WBS) was detected in a family with no clinical suspicion of WBS. The prevalence of CMMS was therefore,0.99%.ConclusionThis is the first investigation of a panel of CMMS in a large sample set of "familial ID patients". The findings of this study showed the low prevalence of CMMSs in "familial ID" patients in spite of the significant contribution of such aberrations in "sporadic ID" which has a very useful practical impact by avoiding unnecessary diagnostic tests in "familial ID" patients.

New microdeletion and microduplication syndromes: a comprehensive review

“…Alteration of gene dosage due to gains or deletions of large genomic regions causes many genetic disorders that are frequently associated with intellectual disability (ID), multiple congenital anomalies (MCA), autistic spectrum disorders (ASD) and other phenotypic findings (Lupski and Stankiewicz, 2005) The advances in the use of microarrays for diagnosis and research in genomic disorders has permitted the discovery of infrequent genomic rearrangements in a variety of diseases and the report of several microdeletion and microduplication syndromes (Deak et al , 2011; Rafati et al , 2012; Vissers and Stankiewicz, 2012; Weise et al , 2012…”

Submicroscopic Chromosomal Variations in Children With Idiopathic Intellectual and Developmental Disabilities

“…In this MLPA analysis, we detected two Williams syndromes diagnosed patients with a microdeletion at 7q11.2 for ELN and LIMK1 genes. In a study on familial and sporadic IDs, deletion in both ELN and LIMK1 was detected in an 8-year-old intellectual disabled patient and considered to be a pathogenic marker for Williams-Beuren syndrome [16]. Early studies already implicated that these two genes are important in causing some characteristics of cognitive profiles since the LIMK1 gene is important for long-term memory and synaptic plasticity through transcriptional factor cellular retinol-binding protein in normal individual [17].…”

Novel Insight Into Intellectual Disability; A Review Article

“…It is a lifelong disability that affects about 1% to 3% of the universal population. It imposes a heavy burden on affected families, the society, and the health care system (2,3). Extensive evidence indicated that in particular regions, by consanguinity, recessive mutations have high incidence rates (4).…”