RESUMO
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with genetic and clinical heterogeneity. The interplay of de novo and inherited rare variants has been suspected in the development of ASD. Here, we applied whole exome sequencing (WES) on 19 trios from singleton Saudi families with ASD. We developed an analysis pipeline that allows capturing both de novo and inherited rare variants predicted to be deleterious. A total of 47 unique rare variants were detected in 17 trios including 38 which are newly discovered. The majority were either autosomal recessive or X-linked. Our pipeline uncovered variants in 15 ASD-candidate genes, including 5 (GLT8D1, HTATSF1, OR6C65, ITIH6 and DDX26B) that have not been reported in any human condition. The remaining variants occurred in genes formerly associated with ASD or other neurological disorders. Examples include SUMF1, KDM5B and MXRA5 (Known-ASD genes), PRODH2 and KCTD21 (implicated in schizophrenia), as well as USP9X and SMS (implicated in intellectual disability). Consistent with expectation and previous studies, most of the genes implicated herein are enriched for biological processes pertaining to neuronal function. Our findings underscore the private and heterogeneous nature of the genetic architecture of ASD even in a population with high consanguinity rates.
Assuntos
Transtorno do Espectro Autista/genética , Sequenciamento do Exoma , Mutação/genética , Consanguinidade , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Transtornos do Neurodesenvolvimento/genética , Arábia Saudita/epidemiologiaRESUMO
Autistic spectrum disorder (ASD) is a complex neurodevelopmental disorder that results in social and communication impairments, as well as repetitive and stereotyped patterns. Genetically, ASD has been described as a multifactorial genetic disorder. The aim of the present study was to investigate possible susceptibility loci of ASD, utilizing the highly consanguineous and inbred nature of numerous families within the population of Saudi Arabia. A total of 13 multiplex families and 27 affected individuals were recruited and analyzed using Affymetrix GeneChip(®) Mapping 250K and 6.0 arrays as well as Axiom arrays. Numerous regions of homozygosity were identified, including regions in genes associated with synaptic function and neurotransmitters, as well as energy and mitochondria-associated genes, and developmentally-associated genes. The loci identified in the present study represent regions that may be further investigated, which could reveal novel changes and variations associated with ASD, reinforcing the complex inheritance of the disease.
Assuntos
Transtorno do Espectro Autista/genética , Consanguinidade , Loci Gênicos , Predisposição Genética para Doença , Genoma Humano , Homozigoto , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/patologia , Mapeamento Cromossômico , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Padrões de Herança , Masculino , Análise em Microsséries , Mitocôndrias/genética , Mitocôndrias/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Linhagem , Arábia Saudita , Transmissão Sináptica/genéticaRESUMO
The insertion of sewing needles into the abdominal cavity is an uncommon form of child abuse. We report a 2-and-a-half-year-old boy with 2 intra-abdominal sewing needles that were discovered during the evaluation of chronic abdominal pain and vomiting. This case report illustrates the wide range with which abusive injury can present in children. Pediatricians need to be alerted to this newly-recognized and the increasing form of child abuse so that they examine and diagnose their patients appropriately.