Systematic analysis of inheritance pattern determination in genes that cause rare neurodevelopmental diseases.

Autor:	Park S; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, South Korea., Jang SS; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, South Korea., Lee S; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, South Korea.; Department of Genomic Medicine, Seoul National University Hospital, Seoul, South Korea., Kim M; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea., Sim H; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea., Jeon H; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea., Hong SE; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea., Lee J; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea., Lee J; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea., Jeon EY; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea., Lee J; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea., Lee CR; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea., Kim SY; Department of Genomic Medicine, Seoul National University Hospital, Seoul, South Korea., Kim MJ; Department of Genomic Medicine, Seoul National University Hospital, Seoul, South Korea.; Rare Disease Center, Seoul National University Hospital, Seoul, South Korea., Yoon JG; Department of Genomic Medicine, Seoul National University Hospital, Seoul, South Korea., Lim BC; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, South Korea., Kim WJ; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, South Korea., Kim KJ; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, South Korea., Ko JM; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, South Korea., Cho A; Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, South Korea., Lee JS; Department of Pediatrics, Seoul National University Hospital Child Cancer and Rare Disease Administration, Seoul National University Children's Hospital, Seoul, South Korea., Choi M; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea., Chae JH; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, South Korea.; Department of Genomic Medicine, Seoul National University Hospital, Seoul, South Korea.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2022 Sep 12; Vol. 13, pp. 990015. Date of Electronic Publication: 2022 Sep 12 (Print Publication: 2022).
DOI:	10.3389/fgene.2022.990015
Abstrakt:	Despite recent advancements in our understanding of genetic etiology and its molecular and physiological consequences, it is not yet clear what genetic features determine the inheritance pattern of a disease. To address this issue, we conducted whole exome sequencing analysis to characterize genetic variants in 1,180 Korean patients with neurological symptoms. The diagnostic yield for definitive pathogenic variant findings was 50.8%, after including 33 cases (5.9%) additionally diagnosed by reanalysis. Of diagnosed patients, 33.4% carried inherited variants. At the genetic level, autosomal recessive-inherited genes were characterized by enrichments in metabolic process, muscle organization and metal ion homeostasis pathways. Transcriptome and interactome profiling analyses revealed less brain-centered expression and fewer protein-protein interactions for recessive genes. The majority of autosomal recessive genes were more tolerant of variation, and functional prediction scores of recessively-inherited variants tended to be lower than those of dominantly-inherited variants. Additionally, we were able to predict the rates of carriers for recessive variants. Our results showed that genes responsible for neurodevelopmental disorders harbor different molecular mechanisms and expression patterns according to their inheritance patterns. Also, calculated frequency rates for recessive variants could be utilized to pre-screen rare neurodevelopmental disorder carriers. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest (Copyright © 2022 Park, Jang, Lee, Kim, Sim, Jeon, Hong, Lee, Lee, Jeon, Lee, Lee, Kim, Kim, Yoon, Lim, Kim, Kim, Ko, Cho, Lee, Choi and Chae.)
Databáze:	MEDLINE
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