Compound Homozygous Rare Mutations in PLCE1 and HPS1 Genes Associated with Autosomal Recessive Retinitis Pigmentosa in Pakistani Families.

Autor:	Babar ME; The University of Agriculture, Dera Ismail Khan, Pakistan., Ali A; Department of Biotechnology, Virtual University of Pakistan, Lahore, Pakistan., Abbas SH; Department of Bioinformatics & Computational Biology, Virtual University of Pakistan, Lahore, Pakistan., Hasnain MJU; Department of Bioinformatics & Computational Biology, Virtual University of Pakistan, Lahore, Pakistan., Babar N; Resident Histopathology, Shaukat Khanum Memorial Hospital, Lahore, Pakistan., Babar H; Resident Hematology, Mayo Hospital, Lahore, Pakistan., Hussain T; Department of Molecular Biology, Virtual University of Pakistan, Lahore, Pakistan., Nadeem A; Department of Molecular Biology, Virtual University of Pakistan, Lahore, Pakistan., Ayub N; Department of Biotechnology, Virtual University of Pakistan, Lahore, Pakistan., Shahid S; Department of Biotechnology, Virtual University of Pakistan, Lahore, Pakistan., Pervez MT; Department of Bioinformatics & Computational Biology, Virtual University of Pakistan, Lahore, Pakistan.
Jazyk:	angličtina
Zdroj:	Iranian journal of public health [Iran J Public Health] 2022 Sep; Vol. 51 (9), pp. 2048-2059.
DOI:	10.18502/ijph.v51i9.10560
Abstrakt:	Background: Retinitis pigmentosa (RP) belongs to pigmentary retinopathies, a generic name for all retinal dystrophies with a major phenotypical and genotypical variation, characterized by progressive reduction of photo-receptor functionality of the rod and cone. Global prevalence of RP is ~ 1/4000 and it can be inherited as autosomal dominant (adRP), autosomal recessive (arRP) or X- linked (xlRP). We designed this study to identify causative mutations in Pakistani families affected with arRP. Methods: In 2019, we recruited two unrelated Pakistani consanguineous families affected with progressive vision loss and night blindness from Punjab region. Clinical diagnosis confirmed the; bone spicule pigmentation of the retina, and an altered electroretinogram (EGR) response. Proband and healthy individual from each family were subjected for whole-exome sequencing (WES). Various computational tools were used to analyze the Next Generation Sequencing (NGS) data and to predict the pathogenicity of the identified mutations. Results: WES data analysis highlighted two missense homozygous variants at position c.T1405A (p.S469T) in PLCE1 and c.T11C (p.V4A) in HPS1 genes in proband of both families. Healthy individuals of two families were tested negative for p.S469T and p.V4A mutations. The variant analysis study including molecular dynamic simulations predicted mutations as disease causing. Conclusion: Compound effect of mutations in rarely linked PLCE1 and HPS1 genes could also cause RP. This study highlights the potential application of WES for a rapid and precise molecular diagnosis for heterogeneous genetic diseases such as RP. (Copyright © 2022 Babar et al. Published by Tehran University of Medical Sciences.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu