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- Title
Exome sequencing identifies homozygous variants in MBOAT7 associated with neurodevelopmental disorder.
- Authors
Nazmina, Gul; Khan, Amjad; Jiang, Jiuhong; Miao, Zhichao; Khan, Shahid Niaz; Khan, Muhammad Ismail; Shah, Abdul Haleem; Shah, Ayesha Haleem; Khisroon, Muhammad; Haack, Tobias B
- Abstract
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.
- Subjects
RECESSIVE genes; SELF-injurious behavior; NEURAL development; CONGENITAL disorders; DEVELOPMENTAL delay; MISSENSE mutation
- Publication
Clinical Genetics, 2024, Vol 105, Issue 4, p423
- ISSN
0009-9163
- Publication type
Article
- DOI
10.1111/cge.14469