Whole-Exome Sequencing of Pakistani Consanguineous Families Identified Pathogenic Variants in Genes of Intellectual Disability

Maria Asif; Maryam Anayat; Faiza Tariq; Tanzeela Noureen; Ghulam Naseer Ud Din; Christian Becker; Kerstin Becker; Holger Thiele; Ehtisham Ul Haq Makhdoom; Pakeeza Arzoo Shaiq; Shahid M Baig; Peter Nürnberg; Muhammad Sajid Hussain; Ghazala Kaukab Raja; Uzma Abdullah

doi:10.3390/genes14010048

Whole-Exome Sequencing of Pakistani Consanguineous Families Identified Pathogenic Variants in Genes of Intellectual Disability

Genes (Basel). 2022 Dec 23;14(1):48. doi: 10.3390/genes14010048.

Authors

Maria Asif^{1

2}, Maryam Anayat³, Faiza Tariq³, Tanzeela Noureen³, Ghulam Naseer Ud Din³, Christian Becker¹, Kerstin Becker¹, Holger Thiele¹, Ehtisham Ul Haq Makhdoom^{4

5}, Pakeeza Arzoo Shaiq³, Shahid M Baig^{5

6

7}, Peter Nürnberg^{1

2}, Muhammad Sajid Hussain^{1

2}, Ghazala Kaukab Raja³, Uzma Abdullah³

Affiliations

¹ Cologne Center for Genomics (CCG), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50931 Cologne, Germany.
² Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine and University Hospital Cologne, 50931 Cologne, Germany.
³ University Institute of Biochemistry and Biotechnology (UIBB), PMAS-Arid Agriculture University Rawalpindi (PMAS-AAUR), Rawalpindi 46300, Pakistan.
⁴ Neurochemical Biology and Genetics Laboratory (NGL), Department of Physiology, Faculty of Life Sciences, Government College University, Faisalabad 38000, Pakistan.
⁵ Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE) College, PIEAS, Faisalabad 38000, Pakistan.
⁶ Department of Biological and Biomedical Sciences, The Aga Khan University, Karachi 74800, Pakistan.
⁷ Pakistan Science Foundation (PSF), Islamabad 44050, Pakistan.

Abstract

Intellectual disability (ID) is a condition of significant limitation of cognitive functioning and adaptive behavior, with 50% of etiology attributed to genetic predisposition. We recruited two consanguineous Pakistani families manifesting severe ID and developmental delay. The probands were subjected to whole exome sequencing (WES) and variants were further prioritized based on population frequency, predicted pathogenicity and functional relevance. The WES data analysis identified homozygous pathogenic variants in genes MBOAT7 and TRAPPC9. The pathogenicity of the variants was supported by co-segregation analysis and in silico tool. The findings of this study expand mutation spectrum and provide additional evidence to the role of MBOAT7 and TRAPPC9 in causation of ID.

Keywords: MBOAT7; TRAPPC9; consanguineous; intellectual disability; whole-exome sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Consanguinity
Exome Sequencing
Humans
Intellectual Disability* / genetics
Pakistan
Pedigree

Grants and funding

This work was supported by the Koeln Fortune Program (Faculty of Medicine, University of Cologne; 381/2020 to M.S.H) and the Center for Molecular Medicine Cologne (CMMC) (Projects 38-RP and C12; 2635/8029/01 and 2635/8326/01 to P.N. and M.S.H.).