2023

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Browsing 2023 by Author "Maria Bibi"

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    Identification of deleterious variations causing cognitive impairement
    (UMT, Lhr, 2023) Maria Bibi
    Intellectual developmental disorder is an autosomal recessive disorder with abnormalities in adaptive behavior. Protein arginine methytransferase 7 involved in the methylation of arginine residue in post translational modification. It catalyzes the transfer of methyl group to the nitrogen of arginine residue from s-adenosyl-l-methionine. This translational modification involves in the several biological processes, e.g. mRNA splicing, signal transduction, protein translocation, DNA repair, and transcriptional control. I reported 5 siblings from normal parents and exome sequencing revealed that 14 years old female has novel non-synonymous, homozygous variant chr16 68337521, NM_001184824; c.304G>A; p.Gly102Arg in exon 5 of PRMT7 gene causing a condition known as SBIDDS (short stature, brachydactyl, intellectual, developmental disability seizers) syndrome. In this study further bioinformatics approach has been used to predict the other pathogenic variants besides the results of bench work. The most damaging variants of PRMT7 gene that can affect the functionality and stability of the protein were predicted. The 32 pathogenic variants of missense and 6 of splice sites were retrieved from gnomad and CADD. Further different databases being used for different analysis over missense variants such as functional analysis, stability analysis, and PTM analysis. Splice site analysis also performed by using several databases. UCSF Chimera was used for interactive visualization. A total of three 3 PTM sites were also predictably disrupted by 32 variants. SPICE and HSF 3.1 were applied to 6 filtered variants to check their disease causing potential. My findings further expand the molecular and clinical spectrum of homozygous PRMT7 mutations that confirmed its association with SBIDDS syndrome. Further bioinformatics approach predicted the correlation of different variants and severity of phenotypes. It is expected that an extensive in silico analysis can determine the likely pathogenic variations for further in vitro experimental analysis.