Genetic mutation spectrum of pantothenate kinase-associated neurodegeneration expanded by breakpoint sequencing in pantothenate kinase 2 gene

Abstract

AbstractBackgroundNeurodegeneration with brain iron accumulation describes a group of rare heterogeneous progressive neurodegenerative disorders characterized by excessive iron accumulation in the basal ganglia region. Pantothenate kinase-associated neurodegeneration (PKAN) is a major form of this disease.ResultsA total of 7 unrelated patients were diagnosed with PKAN in a single tertiary center from August 2009 to February 2018. Ten variants inPANK2including three novel sequence variants and one large exonic deletion were detected. Sequencing of the breakpoint was performed to predict the mechanism of large deletion and AluSx3 and AluSz6 were found with approximately 97.3% sequence homology.ConclusionThe findings support the disease-causing role ofPANK2and indicate the possibility that exonic deletion ofPANK2found in PKAN is mediated throughAlu-mediated homologous recombination.