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KMID : 0381120210430050503
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Genes and Genomics
2021 Volume.43 No. 5 p.503 ~ p.512
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Whole exome sequencing revealed novel variants in consanguineous Pakistani families with intellectual disability
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Rasool Iqra Ghulam
Zahoor Muhammad Yasir
Iqbal Muhammad
Anjum Aftab Ahmad
Ashraf Fatima
Abbas Hafiz Qamar
Baig Hafiz Muhammad Azhar
Mahmood Tariq
Shehzad Wasim
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Abstract
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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.
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KEYWORD
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Intellectual disability, Mutations, Pakistani population, Consanguineous, Whole exome sequencing
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