A novel mutation in SETX and ATM causes ataxia in consanguineous Pakistani families | [Pakistan Journal of Medical Sciences • 2024]

Author(s):

1. Rabia Akram: Neurochemicalbiology and Genetics Laboratory (NGL), Faculty of Life Sciences, Government College University, Faisalabad, Pakistan.

2. Shahid Mahmood Baig: Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE) College, Faisalabad, Pakistan. Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.

3. Haseeb Anwar: Neurochemicalbiology and Genetics Laboratory (NGL), Faculty of Life Sciences, Government College University, Faisalabad, Pakistan.

4. Ghulam Hussain: Neurochemicalbiology and Genetics Laboratory (NGL), Faculty of Life Sciences, Government College University, Faisalabad, Pakistan.

Abstract:

Background & Objectives: Ataxia is usually caused by cerebellar pathology or a decrease in vestibular or proprioceptive aferent input to the cerebellum. It is characterized by uncoordinated walking, truncal instability, body or head tremors, uncontrolled coordination of the hands, dysarthria, and aberrant eye movements. The objective of the current investigation was to identify the underlying genetic cause of the hereditary ataxia that afects the Pakistani population. Methods: We studied numerous consanguineous Pakistani families whose members had ataxia-related clinical symptoms to varying degrees. The families were chosen from the Punjab province, and the neurophysician conducted a clinical examination. Peripheral blood samples from both sick and healthy members of the family were taken after obtaining informed consent. Genomic DNA was used to find potential variations in probands using whole exome sequencing. The study was carried out at the University Hospital of Tübingen, Germany, and Government College University in Faisalabad, Pakistan, during 2018-2023. Results: The molecular analysis of these families identified diferent variants including SGCB: c.902C>T, c.668G>A, ATM: c.6196_6197insGAA, SPG11: c.5769del, SETX c.5525_5533del, and ATM: c.7969A>T. A noteworthy mutation in ATM and SETX was observed among them, and its symptoms were shown to cause ataxia in these families. Conclusion: The current study broadens the mutation spectrum of several hereditary ataxia types and suggests the next generation sequencing in conjunction with clinical research for a more accurate diagnosis of overlapping phenotypes of this disorder in the Pakistani population.

Page(s): 1765-1769

DOI: 10.12669/pjms.40.8.9246

Published: Journal: Pakistan Journal of Medical Sciences, Volume: 40, Issue: 8, Year: 2024

Keywords:

Pakistan , Consanguinity , SETX , Spastic paraplegia , Spinocerebellar ataxia , Movement disorders

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