Exome sequencing identifies novel and known mutations in families with intellectual disability

• Main Authors: Memoona Rasheed, Valeed Khan, Ricardo Harripaul, Maimoona Siddiqui, Madiha Amin Malik, Zahid Ullah, Muhammad Zahid, John B. Vincent, Muhammad Ansar
• Format: Article
• Language: English
• Published: BMC 2021-08-01
• Series: BMC Medical Genomics
• Subjects: Intellectual disability; Mutation; Autosomal recessive; Consanguinity
• Online Access: https://doi.org/10.1186/s12920-021-01066-y
• ISSN: 1755-8794

Abstract Background Intellectual disability (ID) is a phenotypically and genetically heterogeneous disorder. Methods In this study, genome wide SNP microarray and whole exome sequencing are used for the variant identification in eight Pakistani families with ID. Beside ID, most of the affected individuals had speech delay, facial dysmorphism and impaired cognitive abilities. Repetitive behavior was observed in MRID143, while seizures were reported in affected individuals belonging to MRID137 and MRID175. Results In two families (MRID137b and MRID175), we identified variants in the genes CCS and ELFN1, which have not previously been reported to cause ID. In four families, variants were identified in ARX, C5orf42, GNE and METTL4. A copy number variation (CNV) was identified in IL1RAPL1 gene in MRID165. Conclusion These findings expand the existing knowledge of variants and genes implicated in autosomal recessive and X linked ID.