De novo duplication on Chromosome 19 observed in nuclear family displaying neurodevelopmental disorders.
Cold Spring Harb Mol Case Stud
; 6(3)2020 06.
Article
em En
| MEDLINE
| ID: mdl-32321736
ABSTRACT
Pleiotropy and variable expressivity have been cited to explain the seemingly distinct neurodevelopmental disorders due to a common genetic etiology within the same family. Here we present a family with a de novo 1-Mb duplication involving 18 genes on Chromosome 19. Within the family there are multiple cases of neurodevelopmental disorders including autism spectrum disorder, attention deficit/hyperactivity disorder, intellectual disability, and psychiatric disease in individuals carrying this copy-number variant (CNV). Quantitative polymerase chain reaction (PCR) confirmed the CNV was de novo in the mother and inherited by both sons. Whole-exome sequencing did not uncover further genetic risk factors segregating within the family. Transcriptome analysis of peripheral blood demonstrated a â¼1.5-fold increase in RNA transcript abundance in 12 of the 15 detected genes within the CNV region for individuals carrying the CNV compared with their noncarrier relatives. Examination of transcript abundance across the rest of the transcriptome identified 407 differentially expressed genes (P-value < 0.05; adjusted P-value < 0.1) mapping to immune response, response to endoplasmic reticulum stress, and regulation of epithelial cell proliferation pathways. 16S microbiome profiling demonstrated compositional difference in the gut bacteria between the half-brothers. These results raise the possibility that the observed CNV may contribute to the varied phenotypic characteristics in family members through alterations in gene expression and/or dysbiosis of the gut microbiome. More broadly, there is growing evidence that different neurodevelopmental and psychiatric disorders can share the same genetic variant, which lays a framework for later neurodevelopmental and psychiatric manifestations.
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Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 19
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Família
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Predisposição Genética para Doença
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Duplicação Gênica
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Estudos de Associação Genética
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Transtornos do Neurodesenvolvimento
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Canadá