Novel homozygous PANK2 mutation identified in a consanguineous Chinese pedigree with pantothenate kinase-associated neurodegeneration

Abstract

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.

The first Vietnamese patient who presented late onset of pantothenate kinase-associated neurodegeneration diagnosed by whole exome sequencing: A case report

“…NBIA caused by PANK2 mutations has been reported previously in Asian ethnic groups, for example, Chinese, Korean, Indian, Iranian, Taiwan, and Thailand. [8,[13][14][15][16][17][18][19][20][21][22][23][24] In this article, we report the first PKAN patient in Vietnam due to the PANK2 mutations.…”

A rare PANK2 deletion in the first north African patient affected with pantothenate kinase associated neurodegeneration

“…They are usually childhood-onset genetic conditions and the majority of affected individuals present with developmental delay, abnormal behavior, progressive cognitive impairment and pyramidal/extrapyramidal movement disruption. Post-mortem pathology highlights axonal swellings with ubiquitinated aggregates, tau tangles or Lewy bodies, depending on the NBIA subtype [1].…”

“…The most common NBIA subtype, accounting for 35-50% of NBIA cases [2,3] is pantothenate kinase-associated neurodegeneration (PKAN) caused by biallelic variants in PANK2 (MIM #606157). PANK2 was the first causal gene discovered in NBIA, with cases reported from nearly all continents [1,[4][5][6][7][8].…”