Familial episodic pain is a rare autosomal-dominant disorder characterized by recurrent attacks of pain. The pathogenesis of familial episodic pain is not very clear so far. Essential tremor is the most common movement disorder, but the identification of essential tremor genes has remained elusive. We studied a four-generation Chinese family with early-onset familial episodic pain and adult onset familial essential tremor. All essential tremor diagnoses were confirmed based on a review of the questionnaires, videotaped neurological examinations and was then reconfirmed by a senior neurologist specializing in movement disorders using published criteria. SCN11A analysis was performed by whole-exome sequencing or Sanger sequencing. We confirmed the presence of the SCN11A (c.673C>T) mutation in family members with episodic pain and essential tremor. We identified a missense mutation of p.Arg225Cys in SCN11A in a four-generation Chinese family with early-onset familial episodic pain and adult onset familial essential tremor syndrome. This may belong to a rare hereditary syndrome that has not been reported up to now. For the first time, we associated the genetic variability of SCN11A with the development of essential tremor, and further confirmed essential tremor is one of the neurological channelopathies.
Leukoencephalopathy with vanishing white matter (VWM) is one of the most prevalent inherited childhood white matter disorders, which caused by mutations in each of the five subunits of eukaryotic translation initiation factor 2B (EIF2B1-5). In our study, 34 out of the 36 clinically diagnosed children (94%) were identified to have EIF2B1-5 mutations by sequencing. 15 novel mutations were identified. CNVs were not detected in patients with only one mutant allele and mutation-negative determined by gene sequencing. There is a significantly higher incidence of patients with EIF2B3 mutations compared with Caucasian patients (32% vs. 4%). c.1037T>C (p.Ile346Thr) in EIF2B3 was confirmed to be a founder mutation in Chinese, which probably one of the causes of the genotypic differences between ethnicities. Our average 4.4 years-follow-up on infantile, early childhood and juvenile VWM children suggested a rapid deterioration in motor function. Episodic aggravation was presented in 90% of infantile cases and 71.4% of childhood cases. 10 patients died during the follow-up. The Kaplan-Meier curve showed that the median survival time is 8.83 ± 1.51 years. This is the largest sample of children in a VWM follow-up study, which is helpful for a more depth understanding about the natural course.
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