New PRPS1 variant p.(Met68Leu) located in the dimerization area identified in a French CMTX5 patient
Autor: | Justine Lerat, Eric Bieth, Hélène Beauvais-Dzugan, Corinne Magdelaine, Anne-Sophie Lia, Paco Derouault, Blandine Acket, Franck Sturtz, Marie-Christine Arne-Bes |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male Models Molecular Pathology Protein Conformation 030105 genetics & heredity Sensorineural deafness Random hexamer Optic neuropathy Charcot-Marie-Tooth Disease Hearing Loss Central Genetics (clinical) Genetic Diseases X-Linked Muscular Disorders Atrophic Pedigree Phenotype NGS Original Article medicine.symptom Polyneuropathy Dimerization Retinitis Pigmentosa Adult medicine.medical_specialty Genotype lcsh:QH426-470 Hearing loss Hearing Loss Sensorineural Charcot‐marie‐tooth 03 medical and health sciences Polyneuropathies Atrophy Optic Atrophies Hereditary deafness Retinitis pigmentosa Genetics medicine Ribose-Phosphate Pyrophosphokinase Humans Molecular Biology Genetic Association Studies PRPS1 business.industry Original Articles medicine.disease lcsh:Genetics 030104 developmental biology Peripheral neuropathy neuropathy business |
Zdroj: | Molecular Genetics & Genomic Medicine, Vol 7, Iss 9, Pp n/a-n/a (2019) Molecular Genetics & Genomic Medicine |
ISSN: | 2324-9269 |
Popis: | Background CMTX5 is characterized by peripheral neuropathy, early‐onset sensorineural hearing impairment, and optic neuropathy. Only seven variants have been reported and no genotype‐phenotype correlations have yet been established. PRPS1 has a crystallographic structure, as it is composed of three dimers that constitute a hexamer. Methods Next‐generation sequencing (NGS) was performed using a custom 92‐gene panel designed for the diagnosis of Charcot‐Marie‐Tooth (CMT) and associated neuropathies. Results We report the case of a 35‐year‐old male, who had presented CMT and hearing loss since childhood associated to bilateral optic neuropathy without any sign of retinitis pigmentosa. A new hemizygous variant on chromosomic position X:106,882,604, in the PRPS1 gene, c.202A > T, p.(Met68Leu) was found. This change is predicted to lead to an altered affinity between the different subunits in the dimer, thereby may prevent the hexamer formation. Conclusion CMTX5 is probably under‐diagnosed, as an overlap among the different features due to PRPS1 exists. Patients who developed polyneuropathy associated to sensorineural deafness and optic atrophy during childhood should be assessed for PRPS1. |
Databáze: | OpenAIRE |
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