Exome sequencing identifies homozygous variants in MBOAT7 associated with neurodevelopmental disorder

Intellectual disability (ID) is a large group of neurodevelopmental disorders characterized by a congenital limitation in intellectual functioning (reasoning, learning, and problem solving), adaptive behavior (conceptual, social, and practical skills), originated at birth and manifested before the age of 18. By whole exome sequencing of five consanguineous Pakistani families presenting hallmark features of ID, global developmental delay, aggressive and self‐injurious behaviors, microcephaly, febrile seizures and facial dysmorphic features, we identified three novel homozygous missense variants (NM_024298.5: c.588G > T; p.Trp196Cys, c.736 T > C; p.Tyr246His and c.524A > C; p. Asp175Ala) and one rare homozygous in‐frame deletion variant (c.758_778del;p.Glu253_Ala259del) in membrane‐bound O‐acyltransferase family member 7 (MBOAT7) gene previously associated with autosomal recessive neurodevelopmental disorder. The segregation of the variants was validated by Sanger sequencing in all family members. In silico homology modeling of wild‐type and mutated proteins revealed substantial changes in the structure of both proteins, indicating a possible effect on function. The identification and validation of new pathogenic MBOAT7 variants in five cases of autosomal recessive ID further highlight the importance of this genes in proper brain function and development. The affected individuals were examined by a local consultant geneticist and medical doctor at district hospital Bannu and Khyber medical university hospital Peshwar. Detailed clinical features including age, gender, family history and consanguinity was recorded. After clinical investigation and consent form, blood samples were collected, then whole exome sequencing was performed and data was analyzed by bioinformatician. Finally, we found a causative variant in three families and submitted to journal of gene medicine for publication.