title: Novel homozygous PANK2 mutation causing atypical pantothenate kinase-associated neurodegeneration (PKAN) in a Cypriot family.
abstract: Pantothenate kinase-associated neurodegeneration (PKAN) is the commonest, recessively inherited form of neurodegeneration with brain iron accumulation (NBIA) resulting from mutations in the pantothenate kinase 2 (PANK2) gene on chromosome 20. PKAN is usually rapidly progressive, presenting in the vast majority in the first decade of life (classic form). A rarer, later onset and slowly progressive (atypical) PKAN form also exists. We present two siblings of Cypriot descent, a 27-year-old man and his clinically asymptomatic younger sister, both of whom were found to be homozygous for a novel c.695A>G (p.Asp232Gly) missense mutation in exon 2 of the PANK2 gene. The index patient presented with a 5-year history of slowly progressive gait disturbance, dysarthria, mild axial rigidity and bradykinesia. His brain MRI scan revealed the characteristic "eye-of-the-tiger" sign. Atypical genetically confirmed PKAN cases are sparsely reported and should be considered in the differential diagnosis of patients presenting with a progressive extrapyramidal syndrome particularly if the radiographic findings are suggestive of iron accumulation. Effective treatment strategies for PKAN are not currently available and symptomatic therapy is often unsatisfactory. However, early diagnosis including the presymptomatic stage is important for genetic counseling and will be crucial for testing novel therapeutics in the future.
authors.affiliation: Clinical Genetics Department, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.
authors.forename: George A
authors.initials: GA
authors.lastname: Tanteles
authors.affiliation: Clinical Genetics Department, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.
authors.forename: Elena
authors.initials: E
authors.lastname: Spanou-Aristidou
authors.affiliation: Neurology Clinics, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.
authors.forename: Chloe
authors.initials: C
authors.lastname: Antoniou
authors.affiliation: Clinical Genetics Department, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.
authors.forename: Violetta
authors.initials: V
authors.lastname: Christophidou-Anastasiadou
authors.affiliation: Neurology Clinics, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus. Electronic address: kleopa@cing.ac.cy.
authors.forename: Kleopas A
authors.initials: KA
authors.lastname: Kleopa
mesh_terms: D000328:Adult; D005192:Family Health; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D006211:Pantothenate Kinase-Associated Neurodegeneration / Q000235:genetics*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase
keywords: NBIA; Neurodegeneration with brain iron accumulation; PANK2; PKAN; Pantothenate kinase 2; Pantothenate kinase-associated neurodegeneration