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Objective:To investigate the clinical characteristics and gene variation of asparagine synthase deficiency that is caused by ASNS gene variation. Methods:In Department of Neuroendocrine Pediatrics, Affiliated Hospital of Qingdao University from October 2018 to February 2020, the clinical data of a family of asparagine synthase deficiency were analyzed retrospectively.The pathogenic mutation of the proband was screened by the full exon analysis technique.The pathogenic sites of candidate genes were determined by combining the phenotype of the proband.In the heterotopic spot of the proband, his parents and other family members were verified by Sanger sequencing.Meanwhile, the relevant literature database was consulted, and the reported ASNS mutation related cases were collected and reviewed. Results:The female with proband visited the hospital at the age of 4 months, and she had recurrent convulsions at the age of about 3 months.Physical examination showed that the child suffered from microcephaly, and mental and motor retardation.Meanwhile, video electroencephalogram examination displayed extensive moderate high amplitude spiny slow wave and sharp slow wave.Exon sequencing illustrated that the compound heterozygous variants of ASNS gene were c. 1211G>A (p.R404H) and c. 1643C>T (p.S548F), respectively.c.1211G>A was a known pathogenic variant, and c. 1643C>T was a new variant.The proband′s younger brother visited the hospital at the age of 2 months, developed convulsions at the age of 1 month, and developed mental and motor retardation.Electroencephalogram displayed that bilateral posterior head was dominant, multiple foci and extensive spike wave, and spike slow wave and fast wave were distributed.Sanger sequencing revealed the same ASNS compound heterozygous variants as the proband.Both of them died of status convulsion at the age of 7 months and 6 months, respectively. Conclusions:This study is helpful to further understand the clinical features of the disease and reveal a new pathogenic mutation of ASNS gene, so as to enrich the mutation spectrum of ASNS gene, thus providing important basis for clinical treatment and genetic counseling.
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OBJECTIVE@#To explore the genetic basis for a child with mental and motor retardation, language impairment, facial dysmorphism and epilepsy.@*METHODS@#Whole exome sequencing was carried out to detect pathogenic variant in the proband, and candidate variant was selected based on his phenotype. Sanger sequencing was used to verify the variant in the proband, his parents and other family members.@*RESULTS@#The proband was found to carry a frameshifting mutation of MBD5 gene, namely c.2217delT (p.F739Lfs*6), which was inherited from his mother and unreported previously. Sanger sequencing confirmed that his brother carried the same mutation with a similar phenotype. His mother also had poor language expression when she was young, in addition with poor academic performance, though she could do some housework and had no history of convulsion.@*CONCLUSION@#A novel pathogenic variant of the MBD5 gene was discovered, which has enriched the mutational spectrum of the MBD5 gene. Above discovery has enabled genetic counseling and prenatal diagnosis for the family.
Subject(s)
Child , Female , Humans , Male , Pregnancy , DNA-Binding Proteins/genetics , Intellectual Disability/genetics , Mutation , Pedigree , Phenotype , Exome SequencingABSTRACT
Objective:To analyze the clinical characteristics of intestinal tuberculosis improving the diagnosis rate of intestinal tuberculosis.Methods:From January 2014 to June 2018, at Wuhan Pulmonary Hospital, the data of clinical symptoms, laboratory examination, imaging, endoscopy, surgery and pathological examination of 205 patients with intestinal tuberculosis were retrospectively analyzed. Descriptive analysis was performed for statistical analysis.Results:Among 205 patients with intestinal tuberculosis, 145 cases were male and 60 cases were female, aged 14 to 85 years old. A total of 189 cases (92.2%) were complicated with lung tuberculosis, of which 151 cases (79.9%) were positive for sputum acid fast staining. A total of 126 cases were tested for feces acid fast staining, of which 83 cases (65.9%) were positive. A total of 60 cases (29.3%) were tested for GeneXpert Mycobacterium tuberculosis/rifampicintablet (GeneXpert MTB/RIP), of which 49 cases (81.7%) were positive. A total of 44 cases of intestinal tuberculosis were diagnosed by biopsy under electronic enteroscopy, and 21 cases were pathologically diagnosed with intestinal tuberculosis after surgical resection. The 21 patients were tested for GeneXpert MTB/RIP, of which 19 cases (90.5%) were positive and 10 cases (47.6%) were positive for tuberculin test. Six patients were clinically diagnosed with intestinal tuberculosis after effective treatment of antituberculosis drugs. Conclusions:Combination of clinical symptoms and laboratory, imaging, endoscopic and pathological examination, as well as the therapeutic effect of diagnostic antituberculosis treatment could make comprehensive diagnosis of intestinal tuberculosis. The GeneXpert MTB/RIP examination is of great value in the diagnosis of intestinal tuberculosis.
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Objective To analyze the clinical characteristics and therapy of levofloxacin-induced prolonged Q-T interval in patients with multi-drug resistant tuberculosis ( MDR-TB) . Methods Clinical materials of 6 patients with MDR-TB who developed prolonged Q-T/QTc interval caused by levofloxacin therapy were analyzed. Those cases were collected from the Tuberculosis Prevention and Control of Wuhan City form April 2010 to August 2014. Results The proportion of patients with levofloxacin-induced prolonged Q-T interval was approximately 3.0%.The condition occurred 2-8 months after the administration. The initial value of QTc interval ranged from 397 ms to 439 ms, while the average was (410.17±14.62) ms.The value of QTc interval was extended to 470-486 ms after treatment of levofloxacin, while the average was (476.33±6.16) ms.The increase of QTc interval was 47-85 ms, while the average was ( 66 ± 11. 48 ) ms. None of them developed Tdp. Conclusion The application of high dosage and long treatment course of levofloxacin in patients with MDR-TB could result in the extension of the Q-T/QTc interval, which should arouse our serious attention. In order to detect the abnormal Q-T/QTc interval in early stage, electrolyte level examination as well as ECG examination should be considered as routine tests before initiation of treatment and during the follow-up treatment.