A family of Niemann-Pick disease type C caused by compound heterozygous mutations in NPC1 gene / 中华神经科杂志

Objective:To report the clinical and genetic characteristics of a family with Niemann-Pick disease type C caused by novel compound heterozygous mutations in the NPC1 gene to improve the clinicians′ recognition of the disease. Methods:Two patients from the family with non-consanguineous marriages admitted to the Department of Neurology of the First Affiliated Hospital of Kunming Medical University in 2020 were examined in detail. Peripheral blood DNA was extracted, and whole exome sequencing was performed on the patients, combined with Sanger sequencing for verification. The mutation and protein function predictor softwares were applied to analyze the mutation sites.Results:The inheritance was autosomal recessive in this family. The onset age of the proband was 9 years, and the main clinical manifestations were dysarthria, dysphagia, cognitive impairment, ataxia, bilateral pyramidal tract impairment, vertical supranuclear gaze palsy and splenomegaly. The clinical phenotype of the proband′s younger brother was similar to that of the proband, but it was more severe than that of the proband. The younger brother of the proband had an earlier age of onset and severe psychomotor retardation. Whole exome sequencing showed that both brothers carried 2 rare variants of NPC1 gene:1 pathogenic, stop gain at c.352_353del, p.Gln119ValfsTer8, and a missense change, c.593A>G, p.Asn198Ser, of suspected pathogenic. Sanger sequencing confirmed that compound heterozygous mutations were derived from the proband′s parents. According to the American College of Medical Genetics and Genomics guidelines, the above variants were rated as pathogenic and suspected pathogenic, respectively. And the c.593A>G, p.Asn198Ser mutation found in this family was a novel one which had not been reported yet. The proband had delayed diagnosis for 7 years from the onset of symptoms. After taking megastat for 1 year, the symptoms of dysphagia, ataxia and vertical eye movement disorder were significantly improved. Conclusions:The clinical phenotype of the pedigree was consistent with the clinical phenotype of Niemann-Pick disease type C. Compound heterozygous mutations of NPC1 gene (c.352_353del; c.593A>G) were found to be the genetic cause of the family.

Back-forward bending CT in simulated surgical position to evaluate the remaining real angle and flexibility of thoracolumbar kyphosis secondary to old osteoporotic vertebral compression fracture / 中国修复重建外科杂志

OBJECTIVE@#To introduce a scout view scanning technique of back-forward bending CT (BFB-CT) in simulated surgical position for evaluating the remaining real angle and flexibility of thoracolumbar kyphosis secondary to old osteoporotic vertebral compression fracture.@*METHODS@#A total of 28 patients with thoracolumbar kyphosis secondary to old osteoporotic vertebral compression fracture who met the selection criteria between June 2018 and December 2021 were included in the study. There were 6 males and 22 females with an average age of 69.5 years (range, 56-92 years). The injured vertebra were located at T 10-L 2, including 11 cases of single thoracic fracture, 11 cases of single lumbar fracture, and 6 cases of multiple thoracolumbar fractures. The disease duration ranged from 3 weeks to 36 months, with a median of 5 months. All patients received examinations of BFB-CT and standing lateral full-spine X-ray (SLFSX). The thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), local kyphosis of injured vertebra (LKIV), lumbar lordosis (LL), and the sagittal vertical axis (SVA) were measured. Referring to the calculation method of scoliosis flexibility, the kyphosis flexibility of thoracic, thoracolumbar, and injured vertebra were calculated respectively. The sagittal parameters measured by the two methods were compared, and the correlation of the parameters measured by the two methods was analyzed by Pearson correlation.@*RESULTS@#Except LL ( P>0.05), TK, TLK, LKIV, and SVA measured by BFB-CT were significantly lower than those measured by SLFSX ( P<0.05). The flexibilities of thoracic, thoracolumbar, and injured vertebra were 34.1%±18.8%, 36.2%±13.8%, and 39.3%±18.6%, respectively. Correlation analysis showed that the sagittal parameters measured by the two methods were positively correlated ( P<0.001), and the correlation coefficients of TK, TLK, LKIV, and SVA were 0.900, 0.730, 0.700, and 0.680, respectively.@*CONCLUSION@#Thoracolumbar kyphosis secondary to old osteoporotic vertebral compression fracture shows an excellent flexibility and BFB-CT in simulated surgical position can obtain the remaining real angle which need to be corrected surgically.

Analysis of CLCN1 gene mutations in a family affected with myotonia congenita / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutations of chloride channel l (CLCN1) gene in a family affected with myotonia congenita.</p><p><b>METHODS</b>Clinical data of the proband and her parents and brother was collected. The coding regions of the CLCN1 gene were subjected to PCR and Sanger sequencing.</p><p><b>RESULTS</b>Two missense mutations (c.937G>A and c.1205C>T), which were respectively located within exons 8 and 11 of the CLCN1 gene, were identified in the proband. The mother and father of the proband were found to harbor the c.937G>A and c.1205C>T mutation, respectively, whilst neither mutation was found in her brother.</p><p><b>CONCLUSION</b>The novel missense CLCN1 mutations probably underlie the disease in this family. These have enriched the spectrum of CLCN1 mutations and may facilitate further research on this disorder.</p>

Mutation (Thr704Met) of the SCN4A gene causes severe familial hypokalemic periodic paralysis / 中华神经科杂志

Objective To investigate the clinical features and pathogenic genes of a familial hypokalemic periodic paralysis ( HOKPP).Methods PCR amplification and DNA sequencing were used to screen candidate genes of the HOKPP family members (CACNA1S, SCN4A, KCNE3), and the clinical features were carefully analyzed at the same time.Results The sequencing analyses of the SCN4A gene in the proband identified three nucleotide sequence mutations, which influenced the amino acid sequence of the skeletal sodium channel.One of the mutations was identified as a C/T heterozygous pattern at the 2111th nucleotide position in exon 13, resulting in a change from Thr to Met at the 704th amino acid position of the sodium channel protein.All affected patients carried the Thr704Met mutation, whereas unaffected family members did not.Clinical symptoms in this family followed an autosomal dominant inheritance pattern.Muscles weakness, pain and hypokalemia in the period between attacks were seen in all patients.Paralytic symptoms occurred early, lasted longer and recurred frequently, while cold was the main predisposing factor.With the progress of the disease, patients represented persistent weakness and atrophy in proximal muscles.Conclusions Mutation (Thr704Met) in the SCN4A gene should be responsible for this family.This mutation causes severe HOKPP and progressive muscle atrophy.

Clinical and genetic study of a family affected with spinocerebellar ataxia 3 and polycystic kidney disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate clinical features and genetic mutations of a family affected with spinocerebellar ataxia 3 and polycystic kidney disease.</p><p><b>METHODS</b>Polymerase chain reaction and DNA sequencing were employed to analyze exon 10 of the SCA3 gene, in addition with all exons and flanking sequences of PKD1 and PKD2 genes. The clinical features were also carefully analyzed.</p><p><b>RESULTS</b>The numbers of CAG repeat in the proband's SCA3 gene were 28/76, with the number of repeats in the mutant allele being in the full range. The sequence of exon 23 of the PKD1 gene was also found to be abnormal. Clinical symptoms of the proband were very serious, which were characterized by obvious ataxia, pyramidal signs, Meige syndrome, depression and high blood pressure.</p><p><b>CONCLUSION</b>Hereditary spinocerebellar ataxia 3 and autonomic dominant polycystic kidney disease may co-occur, and genetic testing is the primary means of diagnosis.</p>

Clinical features and genetic mutation analysis of spinocerebellar ataxias in Yunnan region / 中华神经科杂志

Objective To identify the specific genotype and analyze clinical features of spinocerebellar ataxias (SCAs) pedigree in the region of Yunnan Province.Methods Fourteen SCAs pedigrees and 183 blood samples of the family members were collected between January 2011 and July 2014 from Department of Neurology,First Affiliated Hospital of Kunming Medical College.Polymerase chain reaction (PCR) amplification,agarose gel electrophoresis and DNA sequencing technologies were utilized to identify the specific genotype of SCAs pedigree.Presymptomatic tests were carried out and the clinical features and genetic test results of patients were carefully analyzed.Results SCA3 was the most common subtype of SCAs in the Han nationality of Yunnan region.Nine of the 14 families were SCA3,only one family was SCA2.Additionally,there were four SCAs families that remained indeterminate.The patients with di-allele mutations (46/77) of SCA3 gene had early onset,rapid progression and serious clinical symptoms.Hereditary SCA3 and autonomic dominant polycystic kidney disease can happen simultaneously in a family.The proband SCA3 gene' s CAG repeat number is 28/76,and repetitions of the mutation allele are in all range.The PKD1 gene exon 23 is found to be in abnormal sequence.Conclusions SCA3 is the most common subtype of SCAs in the Han population of Yunnan region.There are 15/46 incomplete penetrance nutation and 46/77 di-allele mutations.It is possible that di-allele mutations make the disease worse and accelerate clinical course progression.SCA3 and polycystic kidney disease can uncommonly happen simultaneously in a family,which perhaps suggests there are interactions between the two disease-virulence genes.

Risk factors and etiology for ischemic stroke in young adults / 国际脑血管病杂志

Ischemic stroke is a catastrophic event in young adults. It may cause death,disability, incapacity and decline in the quality of life. When the neurologists are facing the suspected ischemic stroke in young adults, the greatest challenge of diagnosis is to identify the causes. This article reviews the risk factors, etiological diagnosis as well as its associated disorders and dysfunction in young adults.