Functional study and pathogenicity classification of PRRT2 missense variants in PRRT2-related disorders.

Abstract:

AIMS:PRRT2 variants are associated with various paroxysmal disorders. To date, more than 90 PRRT2 variants have been reported in PRRT2-related disorders. Lack of functional study in majority of missense variants makes their pathogenicity uncertain. We aim to evaluate the clinical significance of PRRT2 missense variants by performing in vitro experiments. METHODS:We systematically reviewed PRRT2-related disorders and summarized reported PRRT2 missense variants. Protein expression and subcellular localization of mutant PRRT2 were investigated in mammal cells. American College of Medical Genetics and Genomics (ACMG) guidelines were used to analyze the pathogenicity of PRRT2 missense variants. RESULTS:A total of 29 PRRT2 missense variants were identified in PRRT2-related disorders. Ten variants were observed to affect both subcellular localization and protein level, three variants only affect membrane localization, and two variants only affect protein level. According to ACMG guidelines, 15 variants were finally classified as "likely pathogenic", three as "benign", three as "likely benign", and eight as "uncertain significance" variants. The likely pathogenic variants were concentrated in the C-terminal of PRRT2. CONCLUSIONS:The pathogenicity of eight uncertain significance variants needs further investigation. C-terminal of PRRT2 is crucial for its physiological function.

journal_name

CNS Neurosci Ther

authors

Zhao SY,Li LX,Chen YL,Chen YJ,Liu GL,Dong HL,Chen DF,Li HF,Wu ZY

doi

10.1111/cns.13147

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

39-46

issue

1

eissn

1755-5930

issn

1755-5949

journal_volume

26

pub_type

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