A de novo ARIH2 gene mutation was detected in a patient with autism spectrum disorders and intellectual disability.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Autism Spectrum Disorder*/genetics ; Intellectual Disability*/genetics ; Ubiquitin-Protein Ligases*/genetics ; Mutation*; Humans ; Male ; Exome Sequencing ; Female ; Genetic Predisposition to Disease ; Child

E3 ubiquitin protein ligase encoded by ARIH2 gene catalyses the ubiquitination of target proteins and plays a crucial role in posttranslational modifications across various cellular processes. As prior documented, mutations in genes involved in the ubiquitination process are often associated with autism spectrum disorder (ASD) and/or intellectual disability (ID). In the current study, a de novo heterozygous mutation was identified in the splicing intronic region adjacent to the last exon of the ARIH2 gene using whole exome sequencing (WES). We hypothesize that this mutation, found in an ASD/ID patient, disrupts the protein Ariadne domain which is involved in the autoinhibition of ARIH2 enzyme. Predictive analyses elucidated the implications of the novel mutation in the splicing process and confirmed its autosomal dominant inheritance model. Nevertheless, we cannot exclude the possibility that other genetic factors, undetectable by WES, such as mutations in non-coding regions and polygenic risk in inter-allelic complementation, may contribute to the patient's phenotype. This work aims to suggest potential relationship between the detected mutation in ARIH2 gene and both ASD and ID, even though functional studies combined with new sequencing approaches will be necessary to validate this hypothesis.
(© 2024. The Author(s).)

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Keywords: Autism spectrum disorder; Autosomal dominant inheritance model; E3 ubiquitin-protein ligase; Splicing region; Ubiquitination; Whole exome sequencing

EC 2.3.2.27 (Ubiquitin-Protein Ligases)

Date Created: 20240709 Date Completed: 20240709 Latest Revision: 20240805

20240805

PMC11233510

10.1038/s41598-024-66475-2

38982159