A Case with a Ring Chromosome 13 in a Cohort of 203 Children with Non-Syndromic Autism and Review of the Cytogenetic Literature

Abstract

Autistic spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by impairments of social interaction, communication and restricted, repetitive and stereotyped patterns of behavior, interests and activities. Frequencies of chromosomal abnormalities in cohorts of individuals with ASD varying between 1.2 and 28.6% have been reported. In this study, we evaluated 203 Thai children who met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), for autistic disorder or pervasive developmental disorder not otherwise specified (PDD-NOS), and who had neither major dysmorphic features nor CGG repeat expansions of the FMR1 gene. A routine G-banding chromosome analysis was performed at a minimum of ISCN 400-550 bands. A chromosomal abnormality was observed in one child (0.5%), a 41-month-old boy with a ring chromosome 13 detected by G-banding analysis and subsequently confirmed by FISH. SNP microarray analysis detected a 2.11-Mb deletion of chromosome 13q34, encompassing 23 genes. The MCF2L and UPF3A genes are among those genes that may explain the autistic features in our case. To the best of our knowledge, only one autistic case with a ring chromosome 13 has been previously reported. In this article, we also systemically reviewed 21 studies that utilized a conventional cytogenetic method to detect chromosomal abnormalities in patients with ASD. When we summed all cases with chromosomal abnormalities, including the case from our study, the frequency of chromosomal abnormalities detected by conventional cytogenetics in patients with ASD was 3.2% (118/3,712).

Towards New Approaches to Evaluate Dynamic Mosaicism in Ring Chromosome 13 Syndrome

“…In fact, a-CGH was a determinant to accurately address the size of deletions in probands. Data obtained directly correlated to the severity of patient's clinical ndings, as reported elsewhere [2,13,[15][16][17].…”

“…Microcephaly was a condition observed in all probands in this study and is a common nding in patients with 13q deletions [13,14,24]. A minimal critical deletion for this trait was determined for 13q34 [2,17]. Although a gene could apparently lack a causative link to a phenotypic trait, one cannot exclude its involvement in that feature.…”

“…Studies of genotype-phenotype correlation delineate the 13q-syndrome and thus provide an e ective understanding of that clinical entity [2,[12][13][14][15][16][17]. Identi cation of speci c genes and their respective association to clinical traits has led, for instance, to the establishment of ZIC2 as a hallmark in cases of 13q-, due to the fact that this gene loss is causative of holoprosencephaly [18].…”

Mapping the genetics of neuropsychological traits to the molecular network of the human brain using a data integrative approach

“…CNTN5 mediates cell surface interactions during nervous system development and play a role in axon connections (Oguro-Ando et al, 2017). MCF2L encodes Rho guanine nucleotide exchange factor (GEF) and is expressed in the human brain (Charalsawadi et al, 2014). The identified top three most significant hits from MAGMA analysis are genes belonging to the S100 family, namely S100A3, S100A4, and S100A5.…”

Chromosomal microarray analysis in a cohort of underrepresented population identifies SERINC2 as a novel candidate gene for autism spectrum disorder

“…Since 2010, chromosomal microarray (CMA) has been recommended as the first-tier clinical diagnostic test for detection of CNVs in patients with ASD, ID, DD and multiple congenital abnormalities (MCA) of unknown causes 4 , 5 . CMA has a much higher diagnostic yield (10–20%) for these individuals than conventional cytogenetics (~3%) 5 – 7 . Most of CMA studies in these disorders have largely focused on Caucasian populations 4 , 8 – 26 .…”