PANK2p.A170fs:a novel pathogenetic mutation, compound withPANK2p.R440P, causing pantothenate kinase Associated neurodegeneration in a Chinese family

Aim Pantothenate kinase associated neurodegeneration (PKAN) is a severe autosomal recessive rare disease and characterized by iron accumulation in the basal ganglia. To investigate the pathogenesis of this disease in two sibling patients with PANK in a Chinese family, whole-exome variant detection and functional analysis were performed. Materials and methods Clinical and radiographic investigations were performed in the two brother patients. Whole exome sequencing (WES) was used in mutation detection, and the mutations were confirmed by Sanger sequencing. A longevity cohort genetic database was applied as Chinese urban controls. Bioinformatic analysis was performed to predict the pathogenicity. Results Compound heterozygous mutations ofPANK2were detected in two sibling brothers with PKAN in a Chinese family: c.510_522del (p.A170fs) and c.1319G > C (p.R440P) in the transcript NM_153638.PANK2: c.510_522del (p.A170fs) was absent in public data and the Chinese urban controls. Bioinformatics analysis showed that the above two variants were pathogenicity. Conclusions We identified a rare compound heterozygous combination ofPANK2mutations found in a Chinese family in which two sibling brothers suffered from PKAN.PANK2c.510_522del (p.A170fs) was the first reported to be a PKAN pathogenic variant.

Automated summary

In this study, whole-exome sequencing and functional analysis were performed to investigate the pathogenesis of PKAN in two siblings from a Chinese family. Compound heterozygous mutations of the PANK2 gene were detected, and one of the mutations was identified as a novel pathogenic variant for PKAN.