title: Novel homozygousPANK2mutation identified in a consanguineous Chinese pedigree with pantothenate kinase-associated neurodegeneration.
abstract: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive neurodegenerative disorder resulting from pantothenate kinase 2 (PANK2) gene mutations. It is clinically characterized by early onset of extrapyramidal symptoms, with or without pigmentary retinopathy, optic atrophy and acanthocytosis. The specific radiographic appearance of PKAN is the eye-of-the-tiger sign. However, there are few studies regarding PKAN patients of Chinese Han ancestry. In the present study, a Chinese 20-year-old female with an 8-year history of unsteady walking and involuntary movements is described. Brain magnetic resonance imaging revealed eye-of-the-tiger sign. Following sequencing of PANK2, a novel homozygous c.863C>T (p.P288L) mutation was identified in the patient and heterozygous c.863C>T was identified in her consanguineous parents. The absence of this mutation in the 1000 Genomes database, The Exome Aggregation Consortium, and 200 controls demonstrated that this mutation was probably pathogenic for PKAN in this family. In addition, the PANK2 c.863C>T mutation was predicted to be deleterious by SIFT, disease causing by Mutation Taster and probably damaging by PolyPhen2.
authors.affiliation: Department of Pediatrics, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Li
authors.affiliation: Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Hong-Fu
authors.initials: HF
authors.lastname: Li
authors.affiliation: Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350004, P.R. China.
authors.forename: Yan-Bin
authors.initials: YB
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Wu
keywords: eye-of-the-tiger sign; homozygous mutation; pantothenate kinase 2; pantothenate kinase-associated neurodegeneration