title: Novel POLG mutations and variable clinical phenotypes in 13 Italian patients.
abstract: 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.
authors.affiliation: Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Da Pozzo
authors.affiliation: Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Cardaioli
authors.affiliation: IRCCS Fondazione Stella Maris, Pisa, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Rubegni
authors.affiliation: Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
authors.forename: Gian Nicola
authors.initials: GN
authors.lastname: Gallus
authors.affiliation: Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Malandrini
authors.affiliation: Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rufa
authors.affiliation: Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Battisti
authors.affiliation: Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
authors.forename: Maria Alessandra
authors.initials: MA
authors.lastname: Carluccio
authors.affiliation: Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Rocchi
authors.affiliation: Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Giannini
authors.affiliation: Department of Neuroscience, Hospital, Arezzo, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Bianchi
authors.affiliation: Department of Neuroscience, Neurological Clinic, University of Pisa, Pisa, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Mancuso
authors.affiliation: Department of Neuroscience, Neurological Clinic, University of Pisa, Pisa, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.affiliation: Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Dotti
authors.affiliation: Department of Medical, Surgical and Neurological Sciences, University of Siena, Viale Bracci 2, 53100, Siena, Italy. federico@unisi.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D009460:Neurologic Examination; D010641:Phenotype; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human
keywords: Clinical phenotypes; DNA polymerase gamma; Genetics; Mitochondrial diseases