PKD is a autosomal dominant hereditary disease with clinical heterogeneity, such as the age of onset, which is typically in childhood or adolescence; range, which is 4 months to 57 years; and clinical features of patients, which varies among individuals, even in the same family [
3]. In this case, the proband harbored a novel mutation from her father, however, her father had almost no clinical symptoms. This example further demonstrated the heterogeneity of the PKD phenotype. Other genetic factors such as pleiotropy might be further analyzed to elucidate the heterogeneity.
PRRT2 has been widely investigated as a causative gene of PKD and many mutations in the
PRRT2 gene are associated with PKD [
9]. In the early literature,
PRRT2 mutations in PKD patients are in three general molecular groups: a) single-base deletions, duplications or substitutions leading to premature termination [
10]; b) missense mutations; and c) microdeletions leading to frameshifts. We found a novel mutation (c.186-187delGC) that was a deletion of two nucleotides, GC, in the coding region of exon 2. The mutation caused a frameshift leading to a premature termination at codon 398.
PRRT2 has 4 exons encoding 340 amino acids and the protein is predicted to have two transmembrane domains of amino acids 269–289 and 318–338 [
8]. However, the truncated protein lacked a proline-rich domain and two transmembrane domains, which might have caused loss of protein function and resulted in location of the protein in the nucleus [
11]. Functional analysis of the truncated protein showed that the mutation did not influence expression. Expression with the wild-type protein indicated that the pathogenic mechanism did not have a dominant negative effect. We think the overexpress of the mutation type will do nothing on the wild type protein by an artificial assay. Based on the experiments performed in vitro, we think that haploinsufficiency is not disputed. And nonsense mediated decay is one of possible mechanism to haploinsufficiency [
12], the mechanism of this mutation needs further investigation. The cause for pathology was loss of function of the mutation protein with the normal protein unable to sustain normal functions, resulting in haploinsufficiency and more research should be done to understand the mechanism. PDK is a paroxysmal neurological disorder disease with a favorable response to the ion-channel blocker carbamazepine at a low dose. PKD is believed to be an ion channelopathy [
13]. As a transmembrane protein,
PRRT2 might be involved in ion channels or regulation of ion channels related to PKD [
14]. The novel mutant protein was located in the nucleus and might influence on the ion channels loss of function.