PRRT2 mutations in a cohort of Chinese families with paroxysmal kinesigenic dyskinesia and genotype–phenotype correlation reanalysis in literatures

Abstract

This study expands the clinical and genetic spectrums of Chinese patients with paroxysmal kinesigenic dyskinesia and infantile convulsions and choreoathetosis. No clear genotype-phenotype correlation between the age at onset and the types of mutations has been determined.

A PRRT2 variant in a Chinese family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures results in loss of interaction with STX1B

“…More than 90 PRRT2 mutations have been identified to date . Moreover, many mutations leading to a premature stop codon produce an unstable mRNA/protein that is rapidly degraded .…”

“…More than 90 PRRT2 mutations have been identified to date. 10 Moreover, many mutations leading to a premature stop codon produce an unstable mRNA/protein that is rapidly degraded. 28 Consistent with previous findings, 28,29 we found that the truncated p.Ser208Ilefs*17-PRRT2 protein was expressed at a significantly lower level than the WT and translocated into the cytoplasm.…”

“…Mutations in PRRT2, KCNA1, SCN8A, and POC1B have been associated with PKD or PKD/BFIS, among which PRRT2 is the major causative gene of PKD, BFIS, and combined PKD and BFIS (known as infantile convulsions and choreoathetosis) . More than 90 mutations in PRRT2 have been identified thus far, and seizure phenotypes such as febrile seizures and epilepsy have also been reported in PRRT2 mutation carriers …”

“…2,3 Mutations in PRRT2, 4,5 KCNA1, 6 SCN8A, 7 and POC1B 8 have been associated with PKD or PKD/BFIS, among which PRRT2 is the major causative gene of PKD, BFIS, and combined PKD and BFIS (known as infantile convulsions and choreoathetosis). 9 More than 90 mutations in PRRT2 have been identified thus far, 10 and seizure phenotypes such as febrile seizures and epilepsy have also been reported in PRRT2 mutation carriers. 9,[11][12][13][14] The PRRT2 protein consists of a large proline-rich domain located in the cytoplasm, a helix-loop-helix (HLH) domain embedded in the inner surface of the plasma membrane, and a transmembrane domain that spans the plasma membrane.…”

Novel mutation of the PRRT2 gene in two cases of paroxysmal kinesigenic dyskinesia: Two case reports

“…At present, mutations of the PRRT2 gene are the major cause of PKD, with a frequency ranging from 40% to >90%, depending on case ascertainment (1,3). The frameshift mutation c.649dupC (p.Arg217Profs*8), which results in the presence of a premature stop codon, is a hotspot mutation (4). In the present report, two cases of sporadic PKD with sequencing analysis of the PRRT2 gene are described, identifying a potentially novel heterozygous missense mutation, c.955G>T (p.Val319Leu), in exon 3 of the PRR2 gene.…”