doiSerbia

Novel PANK2 mutation identified in patient with pantothenate kinase-associated neurodegeneration

Svetel Marina (Neurology Clinic, Clinical Centre of Serbia, Belgrade, Serbia + University of Belgrade, Faculty of Medicine, Belgrade, Serbia)
Novaković Ivana (University of Belgrade, Faculty of Medicine, Institute for Human Genetics, Belgrade, Serbia)
Tomić Svetlana (Josip Juraj Strossmayer University of Osijek, School of Medicine, Osijek University Hospital Center, Clinical Department of Neurology, Osijek, Croatia)
Kresojević Nikola (Neurology Clinic, Clinical Centre of Serbia, Belgrade, Serbia)
Kostić Vladimir (Neurology Clinic, Clinical Centre of Serbia, Belgrade, Serbia + University of Belgrade, Faculty of Medicine, Belgrade, Serbia)

Introduction. Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, recessively inherited disorder caused by mutations in the pantothenate kinase 2 (PANK2) gene on chromosome 20p13. The objective of this report is to present a patient with atypical PKAN with the novel heterozygous PANK2 mutation. Case outline. We present a 32-year-old female who had disease onset at the age 20 (depression, speech, chewing problems and backward falls) with progressive course. Neurological examination revealed hypomimia, risus sardonicus, dysphagia, tachylalia and severe dystonic dysarthria, moderate arms, legs, and jaw-opening dystonia, postural instability, urge incontinence, and decreased visual acuity. Brain magnetic resonance imaging revealed iron accumulation in the bilateral globus pallidus and putamen (“eye-of-the-tiger”), a radiological finding pathognomonic for PKAN. Genetic analysis revealed known mutation p.T528M (c.1583C>T) in exon 6, and novel p.Y405D (c.1213T>G) in exon 3 of the PANK2 gene. In silico analyses strongly suggested this mutation to be pathogenic. Conclusion. We report a patient with PKAN, and novel substitution p.Y405D (c.1213T>G) in PANK2 that has not been previously described in PKAN patients.

Keywords: neurodegeneration with brain iron accumulation, pantothenate kinase-associated neurodegeneration, PANK2