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Evidence of Dual Molecular Diagnosis of a Young Male Patient With Hereditary Spastic Paraplegia Carrying Two Rare Autosomal Mutations

Year: 2025

Type: article

Abstract: Hereditary spastic paraplegia (HSP) is a group of disorders that mostly affect the upper motor neurons of the spinal cord, with varying inheritance patterns and clinical presentations. We present the case of an 18-year-old male patient who was medically evaluated at a recruitment center due to non-specific complaints of joint pain and difficulty breathing over several years, without an established diagnosis or treatment. Physical examination revealed significant asymmetric muscle weakness in both legs and asymmetrical patellar reflexes. The patient was referred to diverse specialists and underwent a series of diagnostic tests, including blood work, serology, electromyography, nerve conduction tests, and magnetic resonance imaging of the brain and spine. No specific pathology related to the patient's symptoms was identified. Genetic testing, however, revealed heterozygous likely pathogenic variants in both ZFYVE27 (c.898-2A>G) and DSTYK (c.1742T>C, p.Leu581Ser) genes, confirming the diagnosis of HSP. This case is notable for the rare occurrence of two distinct, very rare genetic mutations contributing to the pathogenesis of HSP, a situation called dual molecular diagnosis. We report a rare case of HSP dual molecular diagnosis. Both DSTYK and ZFYVE27 act on membrane dynamics, critical in neuronal maintenance and axonal transport, essential processes disrupted in HSP. Further investigation is required to inform about potential interaction and the underlying molecular mechanism. Moreover, from the clinical perspective, the diagnostic workup brings to light the importance of awareness of a relatively rare disease and of thorough and comprehensive medical analysis to evaluate and rule out diverse potential causes.

Source: Cureus

DOI: 10.7759/cureus.90036

Authors: Yossy Machluf, Majd Said, Yigal Chechik, Shifra Ben-Dor, Yoram Chaiter

Institutions: Israel Defense Forces Medical Corps, University of Haifa, Weizmann Institute of Science

Language: English

Topic: Hereditary Neurological Disorders

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

OpenAlex ID: W4414168403