POLG Mutations Are Probably Rare in the Han Chinese Population.

Objective Mutations in polymerase gamma gene (POLG) are believed to be an important cause of early and juvenile onset of non-syndromic intractable epilepsy. The aim of this study is to investigate the incidence/prevalence of POLG pathogenic variants in epilespy patients of Han population through sequencing it.Methods Han Chinese patients with seizures prior valproic acid (VPA) exposure at Shanghai Children's Hospital were collected from 2015 to 2019. The clinical diagnosis was based on the 2014 Consensus Statement of Epilepsy by the International League against Epilepsy (ILAE). Blood sampling were performed before VPA treatment. The POLG gene DNA was sequenced by either the first or the next generation sequencing (NGS). The POLG variant burden was illustrated. Liver functions were tested to describe whether they experienced VPA toxicity.Results Totally 216 Han Chinese patients were included, aged from 1 month to 15 years old, 102 were male and 114 were female. The onset age was 1 month old to 13 years old, and the epilepsy course ranged from 2 weeks to about 3 years. VPA treatment was delivered for the generalized or intractable partial seizures at standard dosage. No patient experienced hepatic toxicity following VPA exposure. DNA sequencing data showed no patient had either a homozygous mutation or compound heterozygous mutation of POLG. Single heterozygous mutations of c.1150G>T and p.D384Y were found in 2 patients, and single heterozygous mutation of c.156_158dupGCA was found in 1 patient. None of these variants showed clinical significance.Conclusions Functional modifying POLG homozygous mutations and compound heterozygous mutations were not detected and VPA toxicity was not seen in the current study. POLG mutation frequency might be rare in Han Chinese, and standard VPA therapeutic dosage might be safe for Han Chinese patients.

Cloning and Distribution of rRP58, A Novel Neuronal Gene.

EST (AW055733) is a 3'-cDNA fragment specially expressed in rat brain. It is homologous to human and mouse RP58 gene, which is a transcriptional repressor gene. Primers were designed based on these two genes, and then two transcripts of rRP58 gene were got from male SD rat using RT-PCR method. The rRP58 protein is a C(2)H(2) type zinc finger protein, containing POZ domain at N-terminal and zinc finger domain (ZFD) at C-terminal. In addition, there is a highly acidic region between POZ and ZFD. POZ and ZFD were cloned, expressed and purified. Then, the antibodies to POZ and ZFD were prepared, and used to analyze distribution of alternative transcripts of rRP58.