Identification of a novel variant in GPR56/ADGRG1 gene through whole exome sequencing in a consanguineous Pakistani family | [Abstract Book on International Conference on Food and Applied Sciences (ICFAS-23) 3-5 August 23 • 2023]

Author(s):

1. Shumaila Zulfiqar: Human Molecular Genetics Laboratory, NIBGE College, PIEAS, Faisalabad, Pakistan; Department of Biotechnology, Kinnaird College for Women, Lahore, Pakistan

2. M. Tariq: Human Molecular Genetics Laboratory, NIBGE College, PIEAS, Faisalabad, Pakistan

3. Shafaq Ramzan: Human Molecular Genetics Laboratory, NIBGE College,PIEAS, Faisalabad,Pakistan

4. Ayaz Khan: Human Molecular Genetics Laboratory, NIBGE College,PIEAS, Faisalabad,Pakistan

5. Muhammad Sher: Human Molecular Genetics Laboratory, NIBGE College, PIEAS, Faisalabad, Pakistan

6. Zafar Ali: Centre for Biotechnology and Microbiology, University of Swat, Swat 19130, Pakistan

7. Niklas Dahl: Department of Immunology, Genetics and Pathology, Uppsala University and Science for Life Laboratory, Box 815, 75108 Uppsala, Sweden

8. Uzma Abdullah: Pakistan Science Foundation (PSF), Islamabad, Pakistan

9. Shahid Mahmood Baig: Human Molecular Genetics Laboratory, NIBGE College, PIEAS, Faisalabad, Pakistan; University Institute of Biochemistry and Biotechnology, PMASAAU Rawalpindi, Pakistan; Pakistan Science Foundation (PSF), Islamabad, Pakistan

Abstract:

GPR56 gene is best known for its pivotal role in cerebral cortical development. Mutations in GPR56 give rise to cobblestone-like brain malformation, white matter changes and cerebellar dysplasia. This study aimed to identify causative variant in a consanguineous family having five individuals affected with developmental delay, mild to severe intellectual disability, speech impairment, strabismus and seizures. Whole exome sequencing was performed to identify mutation in affected individuals. Variants were filtered and further validated by Sanger sequencing and segregation analysis. A novel frameshift variant c.1601dupT leading to p.Ala535GlyfsTer17) was identified in GPR56 gene by whole exome sequencing and subsequent filtering. All five affected individuals were homozygous for the mutant allele while four asymptomatic individuals carried the variant in heterozygous state. Radiological findings of a representative patient presented features of GPR56-associated cobblestone like brain malformation. MRI findings suggested paucity of sulci, dilated ventricular system and brainstem atrophy. The microgyria were observed in a simplified gyral pattern (cobblestone). This single bp insertion, and the consequent frameshift, results in the truncation of GPR56 protein. This could result in a malformed cortex giving the brain a cobblestone like shape. Our study identified a 7th novel frameshift variant from Pakistani population in GPR56 gene, thus broadening mutation spectrum.

Page(s): 98-98

DOI: DOI not available

Published: Journal: Abstract Book on International Conference on Food and Applied Sciences (ICFAS-23) 3-5 August 23, Volume: 0, Issue: 0, Year: 2023

Keywords:

brain malformation , GPR56ADGRG1 gene , cerebellar dysplasia

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