Dopa-responsive dystonia (DRD), also known as Segawa syndrome, is a rare neurotransmitter disease. The decrease in dopamine caused by tyrosine hydroxylase (TH) gene mutation may lead to dystonia, tremor and severe encephalopathy in children. Although the disease caused by recessive genetic mutation of the tyrosine hydroxylase (TH) gene is rare, we found that the clinical manifestations of seven children with tyrosine hydroxylase gene mutations are similar to dopa-responsive dystonia. To explore the clinical manifestations and possible pathogenesis of the disease, we analyzed the clinical data of seven patients. Next-generation sequencing showed that the TH gene mutation in three children was a reported homozygous mutation (c.698G>A). At the same time, two new mutations of the TH gene were found in other children: c.316_317insCGT, and c.832G>A (p.Ala278Thr). We collected venous blood from four patients with Segawa syndrome and their parents for real-time quantitative polymerase chain reaction analysis of TH gene expression. We predicted the structure and function of proteins on the missense mutation iterative thread assembly refinement (I-TASSER) server and studied the conservation of protein mutation sites. Combined with molecular biology experiments and related literature analysis, the qPCR results of two patients showed that the expression of the TH gene was lower than that in 10 normal controls, and the expression of the TH gene of one mother was lower than the average expression level. We speculated that mutation in the TH gene may clinically manifest by affecting the production of dopamine and catecholamine downstream, which enriches the gene pool of Segawa syndrome. At the same time, the application of levodopa is helpful to the study, diagnosis and treatment of Segawa syndrome.
The gene encoding collagen like tail subunit of asymmetric acetylcholinesterase (COLQ) is responsible for the transcription of three strands of collagen of acetylcholinesterase, which is attached to the endplate of neuromuscular junctions. Mutations in the COLQ gene are inherited in an autosomal-recessive manner and can lead to type V congenital myasthenia syndrome (CMS), which manifests as decreased muscle strength at birth or shortly after birth, respiratory failure, restricted eye movements, drooping of eyelids, and difficulty swallowing. Here we reported three variants within COLQ in two unrelated children with CMS. An intronic variant (c.393+1G>A) and a novel missense variant (p.Q381P) were identified as compound heterozygous in a 13-month-old boy, with the parents being carriers of each. An intragenic deletion including exons 14 and 15 was found in a homozygous state in a 12-year-old boy. We studied the relative expression of the COLQ and AChE gene in the probands' families, performed three-dimensional protein structural analysis, and analyzed the conservation of the missense mutation c.1142A>C (p.Q381P). The splicing mutation c.393+1G>A was found to affect the normal splicing of COLQ exon 5, resulting in a 27-bp deletion. The missense mutation c.1142A>C (p.Q381P) was located in a conserved position in different species. We found that homozygous deletion of COLQ exons 14–15 resulted in a 241-bp deletion, which decreased the number of amino acids and caused a frameshift translation. COLQ expression was significantly lower in the probands than in the probands' parents and siblings, while AChE expression was significantly higher. Moreover, the mutations were found to cause significant differences in the predicted three-dimensional structure of the protein. The splicing mutation c.393+1G>A, missense mutation c.1A>C (p.Q381P), and COLQ exon 14–15 deletion could cause CMS.
ObjectiveTo explore the correlation between serum 25-hydroxyvitamin D levels and tic disorders (TDs) in Chinese children.MethodsWe selected 2960 children with TD and 2665 healthy controls, aged 5–14 years, from the Department of Neurology of the Shanghai Children’s Hospital. Serum 25-hydroxyvitamin D levels and degrees of vitamin D deficiency were compared between patients with TD and healthy children.ResultsThe mean serum 25-hydroxyvitamin D level in the TD group was significantly lower than that in the control group (P < 0.001). The proportion of patients with 25-hydroxyvitamin D deficiency in the TD group was significantly higher than that in the control group. However, there was no correlation between 25-hydroxyvitamin D deficiency and the severity of TD. In addition, for age-wise comparison, mean levels of 25-hydroxyvitamin D and its deficiency in the TD group were the most significant in children over 9 years of age.ConclusionThere is a correlation between 25-hydroxyvitamin D deficiency and TD in Chinese children, but not between 25-hydroxyvitamin D deficiency and the severity of TD. There was a correlation between age and deficiency of 25-hydroxyvitamin D; this deficiency was most pronounced among those over the age of 9 years.
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