Novel mutations found in genes involved in global developmental delay and intellectual disability by whole-exome sequencing, homology modeling, and systems biology.

IF 3 4区 医学 Q2 PSYCHIATRY
Nafiseh Moeinifar, Zohreh Hojati
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引用次数: 0

Abstract

Background: Genes associated with global developmental delay (GDD) and intellectual disability (ID) are increasingly being identified through next-generation sequencing (NGS) technologies. This study aimed to identify novel mutations in GDD/ID phenotypes through whole-exome sequencing (WES) and additional in silico analyses.

Material and methods: WES was performed on 27 subjects, among whom 18 were screened for potential novel mutations. In silico analyses included protein-protein interactions (PPIs), gene-miRNA interactions (GMIs), and enrichment analyses. The identified novel variants were further modelled using I-Tasser-MTD and SWISS-MODEL, with structural superimposition performed.

Results: Novel mutations were detected in 18 patients, with 10 variants reported for the first time. Among these, three were classified as pathogenic (DNMT1:c.856dup, KCNQ2:c.1635_1636insT, and TMEM94:c.2598_2599insC), and six were likely pathogenic. DNMT1 and MRE11 were highlighted as key players in PPIs and GMIs. GMIs analysis emphasised the roles of hsa-miR-30a-5p and hsa-miR-185-5p. The top-scoring pathways included the neuronal system (R-HSA-112316, p = 7.73E-04) and negative regulation of the smooth muscle cell apoptotic process (p = 3.37E-06). Homology modelling and superimposition revealed a significant functional loss in the mutated DNMT1 enzyme structure.

Conclusion: This study identified 10 novel pathogenic/likely pathogenic variants associated with GDD/ID, supported by clinical findings and in silico analyses focused on DNMT1 mutations.

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来源期刊
CiteScore
7.00
自引率
3.20%
发文量
73
审稿时长
6-12 weeks
期刊介绍: The aim of The World Journal of Biological Psychiatry is to increase the worldwide communication of knowledge in clinical and basic research on biological psychiatry. Its target audience is thus clinical psychiatrists, educators, scientists and students interested in biological psychiatry. The composition of The World Journal of Biological Psychiatry , with its diverse categories that allow communication of a great variety of information, ensures that it is of interest to a wide range of readers. The World Journal of Biological Psychiatry is a major clinically oriented journal on biological psychiatry. The opportunity to educate (through critical review papers, treatment guidelines and consensus reports), publish original work and observations (original papers and brief reports) and to express personal opinions (Letters to the Editor) makes The World Journal of Biological Psychiatry an extremely important medium in the field of biological psychiatry all over the world.
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