p.A170fs：a novel pathogenetic mutation, compound with p.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 of were 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. : 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 of mutations found in a Chinese family in which two sibling brothers suffered from PKAN. c.510_522del (p.A170fs) was the first reported to be a PKAN pathogenic variant.