Whole exome sequencing revealed novel variants in consanguineous Pakistani families with intellectual disability.

Autor: Rasool IG; Molecular Biology and Forensic Laboratory, Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan., Zahoor MY; Molecular Biology and Forensic Laboratory, Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan. yasir.zahoor@uvas.edu.pk., Iqbal M; Department of Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan., Anjum AA; Institute of Microbiology, University of Veterinary and Animal Sciences, Lahore, Pakistan., Ashraf F; Molecular Biology and Forensic Laboratory, Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan., Abbas HQ; Molecular Biology and Forensic Laboratory, Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan., Baig HMA; Department of Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan., Mahmood T; Department of Statistics and Computer Science, University of Veterinary and Animal Sciences, Lahore, Pakistan., Shehzad W; Molecular Biology and Forensic Laboratory, Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan.
Jazyk: angličtina
Zdroj: Genes & genomics [Genes Genomics] 2021 May; Vol. 43 (5), pp. 503-512. Date of Electronic Publication: 2021 Mar 12.
DOI: 10.1007/s13258-021-01070-7
Abstrakt: Background: Intellectual disability (ID) is a heterogeneous disorder affecting 1-3% of the population. Elucidation of monogenic variants for ID is a current challenge. These variants can be better demonstrated in consanguineous affected families.
Objective: The study was designed to find the genetic variants of ID in consanguineous families.
Methods: We analyzed five unrelated consanguineous Pakistani families affected with ID using whole exome sequencing (WES). Data was analyzed using different bioinformatics tools and software.
Results: We mapped four variants including three novels in four different ID known genes. Each variant is found in a different family, co-segregating with a recessive pattern of inheritance. The novel variants found are; c. 2_4del (p.?) mapped in ROS1 and c. 718G>A (p.Gly240Arg) in GRM1. Another novel causative variant, c.2673del (p.Gly892Aspfs*17) identified in COL18A1 in a recessive form, a gene reported for Knobloch syndrome that manifests ID along with typical retinal abnormalities, and this phenotype was confirmed on reverse phenotyping. A mutation c.2134C>T (p.Arg712*) in TRAPPC9 has been found first time in the homozygous recessive form in our enrolled three affected siblings while it was previously reported in compound heterozygous form in a Caucasian descent. While fifth family remained unsolved.
Conclusion: These mutations in four different genes with a recessive inheritance would be a contribution to the disease variant database of this devastating disorder.
Databáze: MEDLINE
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