Importance and usage of chromosomal microarray analysis in diagnosing intellectual disability, global developmental delay, and autism; and discovering new loci for these disorders

Abstract

BackgroundChromosomal microarray analysis is a first-stage test that is used for the diagnosis of intellectual disability and global developmental delay. Chromosomal microarray analysis can detect well-known microdeletion syndromes. It also contributes to the identification of genes that are responsible for the phenotypes in the new copy number variations.ResultsChromosomal microarray analysis was conducted on 124 patients with intellectual disability and global developmental delay. Multiplex ligation-dependent probe amplification was used for the confirmation of chromosome 22q11.2 deletion/duplication. 26 pathogenic and likely pathogenic copy number variations were detected in 23 patients (18.55%) in a group of 124 Turkish patients with intellectual disability and global developmental delay. Chromosomal microarray analysis revealed pathogenic de novo Copy number variations, such as a novel 2.9-Mb de novo deletion at 18q22 region with intellectual disability and autism spectrum disorder, and a 22q11.2 region homozygote duplication with new clinical features.ConclusionOur data expand the spectrum of 22q11.2 region mutations, reveal new loci responsible from autism spectrum disorder and provide new insights into the genotype–phenotype correlations of intellectual disability and global developmental delay.

Chromosomal microarray analysis of 410 Han Chinese patients with autism spectrum disorder or unexplained intellectual disability and developmental delay

“…Neurodevelopmental disorders (NDDs) are a group of heterogeneous disorders involving developmental dysfunction of the central nervous system, and have an incidence rate of 1–3% in children 1 – 3 . Autism spectrum disorder (ASD) and intellectual disability/developmental delay (ID/DD) are the most common NDDs in children and have shared psychiatric behaviors, clinical manifestations, and risk factors, and impair cognitive functions including learning, sociability, and mood 4 .…”

“…Approximately 50% of autistic cases manifest intellectual disability (ID) 5 , 6 . Developmental delay (DD) is the failure to achieve certain developmental milestones at the appropriate age, involving physical, cognitive, communication, social, emotional, and/or adaptive skills 3 . Both ID (IQ < 70) and DD belong to the clinically heterogeneous NDDs 3 .…”

Genetic Landscape of Dystrofin Gene Deletions and Duplications From Turkey: A Single Center Experience

“…The gold standard method for DMD diagnosis is the MLPA technique, because deletions and duplications are frequently observed in DMD (16). Microarray technology is capable of detecting minor deletions and duplications in single-gene disorders due to high single nucleotide polymorphisms (SNP) and small copy number variations (CNV) (17). Deletions in the dystrophin gene were incidentally detected in four patients who were initially scheduled to undergo microarray testing due to congenital hypotonia, epilepsy, growth retardation, and atypical autism.…”

Identifying and supporting autistic preschoolers and their families

“…22 Chromosomal microarray and fragile X testing is considered best practice for children presenting with developmental delay or intellectual disability, signs of autism and/or congenital abnormalities to investigate the possibility of genetic conditions. 23,24 Examples of genetic conditions associated with autism include tuberous sclerosis and fragile X syndrome. 25 When a child is diagnosed as autistic, referral to a genetic counsellor may be indicated so parents can be counselled regarding the recurrence risk for future children.…”