A case of familial paroxysmal nonkinesigenic dyskinesia due to mutation of the PNKD gene in Chinese Mainland.

Background: Paroxysmal dyskinesia is a rare neurological disorder characterized by paroxysmal movement disorders. Paroxysmal movement disorders include kinesigenic choreoathetosis, nonkinesigenic choreoathetosis or dyskinesia (PNKD), exercise-induced choreoathetosis, and hypnogenic paroxysmal dystonia. There have been some sporadic reports of PNKD occurrences in Chinese Mainland, but none has been reported on familial PNKD. Proband and methods A 32 years old male admitted to the First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China in 2009 with recurrent limb involuntary movements spanning over 30 years was diagnosed with PNKD. Family history was collected to identify if it was a case of familial or sporadic PNKD. Mutation and linkage analysis were performed to identify the pathogenic gene and the localization of the same.

Results: There were five generations of 26 patients, out of which 3 of these patients died. Follow-up was conducted on 17 out of the 23 patients alive and 9 normal family members. The pedigree showed autosomal dominant inheritance, whom could be divided into light, moderate, and severe group according to clinical signs, spontaneous attack and response to drugs. All patients harbored c.20C>T (p.A7V) mutation in exon 1 of the PNKD/MR-1 gene. Preliminary linkage analyses using phenocopy rates of 0.0001 and 0.1 suggested that linkage signal localizes between D2S126 and D2S377. The functional consequence of the mutation in the disease pathogenesis is pending investigation. Conclusions We report the first case of familial paroxysmal non-kinesigenic dyskinesia (PNKD) in Chinese Mainland, which coincidentally is also the largest case of familial PNKD ever reported. This article is part of a Special Issue entitled Brain and Memory.