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

• Published in: Genes Vol. 14; no. 1; p. 48
• Main Authors: Asif, Maria, Anayat, Maryam, Tariq, Faiza, Noureen, Tanzeela, Din, Ghulam Naseer Ud, Becker, Christian, Becker, Kerstin, Thiele, Holger, Makhdoom, Ehtisham Ul Haq, Shaiq, Pakeeza Arzoo, Baig, Shahid M, Nürnberg, Peter, Hussain, Muhammad Sajid, Raja, Ghazala Kaukab, Abdullah, Uzma
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.12.2022; MDPI
• Subjects: Brain; Cognitive ability; consanguineous; Consanguinity; Convulsions & seizures; Etiology; Exome Sequencing; Families & family life; Genes; Genomics; Humans; Intellectual disabilities; intellectual disability; Intellectual Disability - genetics; MBOAT7; Microcephaly; Mutation; Pakistan; Pathogenicity; Pedigree; Proteins; Segregation; TRAPPC9; whole-exome sequencing; Pakistan; TRAPPC9; whole-exome sequencing; MBOAT7; intellectual disability; consanguineous
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes14010048

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 and . 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.