Novel POLG mutations and variable clinical phenotypes in 13 Italian patients
Autor: | Michelangelo Mancuso, Alessandro Malandrini, Maria Teresa Dotti, Amedeo Bianchi, Elena Cardaioli, Gabriele Siciliano, Raffaele Rocchi, Fabio Giannini, Alessandra Rufa, Gian Nicola Gallus, Carla Battisti, Paola Da Pozzo, Anna Rubegni, Maria Alessandra Carluccio, Antonio Federico |
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Rok vydání: | 2017 |
Předmět: |
Adult
Male 0301 basic medicine Mitochondrial DNA medicine.medical_specialty Neurology Adolescent DNA Mutational Analysis Mitochondrial diseases Neurological examination DNA-Directed DNA Polymerase Dermatology Biology White People Young Adult 03 medical and health sciences Epilepsy 0302 clinical medicine DNA polymerase gamma Gene duplication Genetics medicine Humans Muscle Skeletal Gene Aged Neurologic Examination Muscle biopsy medicine.diagnostic_test Clinical phenotypes General Medicine Middle Aged medicine.disease Phenotype Psychiatry and Mental health 030104 developmental biology Italy Mutation Female Neurology (clinical) 030217 neurology & neurosurgery |
Popis: | POLG gene encodes the catalytic subunit of DNA polymerase gamma, essential for mitochondrial DNA (mtDNA) replication and repair. Mutations in POLG have been linked to a spectrum of clinical phenotypes, resulting in autosomal recessive or dominant mitochondrial diseases. These mutations have been associated with heterogeneous phenotypes, presenting with varying severity and at different ages of onset, ranging from the neonatal period to late adult life. We screened 13 patients for POLG mutations. All patients underwent a complete neurological examination, and in most of cases, muscle biopsy was performed. We detected 15 different variations in 13 unrelated Italian patients. Two mutations were novel and mapped in the pol domain (p.Thr989dup and p.Ala847Thr) of the enzyme. We also report new cases carrying controversial variations previously described as incompletely penetrant or a variant of unknown significance. Our study increases the range of clinical presentations associated with mutations in POLG gene, underlining some peculiar clinical features, such as PEO associated with corneal edema, and epilepsy, severe neuropathy with achalasia. The addition of two new substitutions, including the second report of an in-frame duplication, to the growing list of defects increases the value of POLG genetic diagnosis in a range of neurological presentations. |
Databáze: | OpenAIRE |
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