Mutational screening of GDAP1 in dysphonia associated with Charcot-Marie-Tooth disease: clinical insights and phenotypic effects

Manzoor U. Ali A. Ali S.L. Abdelkarem O. Kanwal S. Alotaibi S.S. Baazeem A. Baiduissenova A. Yktiyarov A. Hajar A. Olzhabay A.
December 2023 Springer Science and Business Media Deutschland GmbH

Journal of Genetic Engineering and Biotechnology
2023 #21 Issue 1

Introduction: Mutations in GDAP1 (Ganglioside-induced differentiation-associated protein 1) gene are linked to Charcot-Marie-Tooth disease (CMT), a Heterogenous group of disorders with multiple phenotypes, characterized by peripheral nerve dysfunction that can lead to vocal cord paralysis and diaphragmatic dysfunction. Main body: All three affected children of this chosen family have manifested the same clinical symptoms with progressive weakness, mild sensory impairment, and absent tendon reflexes in their early years. Electrodiagnostic analysis displayed an axonal type of neuropathy in affected patients. Sequencing of the GDAP1 gene was requested for all members of the family. Diagnostic assessments included pulmonary and vocal cord function tests, as well as phrenic and peripheral nerve conduction studies. Pathogenicity of GDAP1 variant p.Pro419Leu with axonal CMT2 and autosomal recessive inheritance was confirmed via in silico analysis. Patients with GDAP1 mutations showed dysphonia, speech difficulties, and the characteristic symptoms of CMT. The severity of symptoms correlated with the presence of a type of GDAP1 mutation. Patients with normal vocal cords and pulmonary function exhibited milder symptoms compared to those with GDAP1 mutations. Our study provides clinical insights into the phenotypic effects of GDAP1 mutations in CMT patients. The findings highlight the adverse clinical course and severe disability associated with GDAP1 mutations, including weak limb and laryngeal muscles. Conclusion: Patients with GDAP1 mutations and autosomal recessive neuropathy present with dysphonia and require interventions such as surgery, braces, physical therapy, and exercise. Early diagnosis and comprehensive clinical evaluations are crucial for managing CMT patients with GDAP1 mutations.

Axonal CMT 2 , Charcot-Marie-Tooth disease , GDAP1 mutations , Vocal cord dysphonia

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Department of Clinical Biochemistry, COMSATS University Islamabad, Sahiwal Campus, Sahiwal, Pakistan
Department of Biochemistry, Abdul wali Khan University Mardan, Mardan, 23200, Pakistan
Department of Chemical Pathology, Medical Research Institute, Alexandria University, Alexandria, Egypt
Department of Biotechnology, College of Science, Taif University, P.O.Box 11099, Taif, 21944, Saudi Arabia
Department of Biology, College of Science, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia
Department of Microbiology and Virology, Astana Medical University, Astana City, 010000, Kazakhstan
Department of Biology, Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakech, Morocco
Department of Otorhinolaryngology, Astana Medical University, Astana City, 010000, Kazakhstan

Department of Clinical Biochemistry
Department of Biochemistry
Department of Chemical Pathology
Department of Biotechnology
Department of Biology
Department of Microbiology and Virology
Department of Biology
Department of Otorhinolaryngology

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