TY - JOUR
T1 - Whole-Exome Sequencing of Pakistani Consanguineous Families Identified Pathogenic Variants in Genes of Intellectual Disability
AU - Asif, Maria
AU - Anayat, Maryam
AU - Tariq, Faiza
AU - Noureen, Tanzeela
AU - Din, Ghulam Naseer Ud
AU - Becker, Christian
AU - Becker, Kerstin
AU - Thiele, Holger
AU - Makhdoom, Ehtisham ul Haq
AU - Shaiq, Pakeeza Arzoo
AU - Baig, Shahid M.
AU - Nürnberg, Peter
AU - Hussain, Muhammad Sajid
AU - Raja, Ghazala Kaukab
AU - Abdullah, Uzma
N1 - Funding Information:
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.).
Publisher Copyright:
© 2022 by the authors.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - MBOAT7
KW - TRAPPC9
KW - consanguineous
KW - intellectual disability
KW - whole-exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85146802614&partnerID=8YFLogxK
U2 - 10.3390/genes14010048
DO - 10.3390/genes14010048
M3 - Article
C2 - 36672789
AN - SCOPUS:85146802614
SN - 2073-4425
VL - 14
JO - Genes
JF - Genes
IS - 1
M1 - 48
ER -