PRRT2 Mutations in Paroxysmal Kinesigenic Dyskinesia with Convulsions in Cohort

PRRT2 mutations in patients with paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC).

Twenty-one different mutations have been identified in PRRT2 in familial and sporadic PKD/IC patients, with the majority resulting in a truncation of the PRRT2 protein. p.R217Efs*12 is particularly common and accounts for 75.5% (71/94) of the patients with PRRT2 mutations. The mutations identified in this study are labeled in red and the novel ones with “#”, and those found in previous studies are labeled in black . Numbers within parentheses denote the number of the patients with the specific mutations.  

The PRRT2 mutations identified in patients with paroxysmal kinesigenic dyskinesia with infantile convulsionin this study.

The PRRT2 heterozygous mutations, (A) c.272delC (p.P91Qfs*24), (B) c.595G>T (p.E199X), (C) c.604_607delTCAC (p.S202Hfs*16), (D) c.649_650insC (p.R217Pfs*8), (E) c.649del (p.R217Efs*12), (F) c.718C>T (p.R240X), and (G) c.922C>G (p.R308C) are shown by sequencing both the mutant and normal strands of the TA-subcloned PCR fragments. 

Haplotype analyses of the patients carrying PRRT2 p.R217Pfs*8 mutation.

Five unrelated PKD/IC pedigrees carry the PRRT2 p.R217Pfs*8. Patients 4 (A), 5 (B), 6 (C), 7 (D), and 8 (E) are indicated with arrows. Asterisks (*) depict the individuals who were haplotyped. The squares and circles denote males and females, and the close and open symbols represent affected and unaffected members, respectively. The grey symbols denote undetermined disease status. The PRRT2 genotype is labeled below the symbols. The alleles with an unknown phase are labeled and separated with a slash. The haplotypes linked to the PRRT2 p.R217Pfs*8 in the seven unrelated index patients are showed in (F). Five patients shared a common haplotype at loci rs9922666, rs7205278, rs4788186, rs7204252, and rs889695 linked to the PRRT2 p.R217Pfs*8 (G-T-p.R217Pfs*8-A-T-T).