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
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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