Construction and Application of National Rare Diseases Registry System of China / 罕见病研究

Rare diseases have been a major challenge for clinical medicine and public health challenge in China. One of the effective measures is to conduct proactive research on rare diseases to deal with the disease burden of the diseases. However, low prevalence, disperse distribution of patients, lack of knowledge about the disease course, and phenotype heterogeneity hamper the development of research for rare diseases. Recently, it has been found that patients registry is effective in understanding the course of the disease and accu- mulating the cases and data of clinical research or clinical trial design. At present, most of developed countries or regions in the world have promoted clinical research and clinical trials of new medications on rare diseases by using the registration of rare disease. In 2016, Peking Union Medical College Hospital established China's first registry system at the national level-National Rare Disease Registry System of China(NRDRS). NRDRS has accumulated 68 137 cases data registered by the researchers from China's 101 collaborating hospitals in 29 provinces/municipalities/autonomous regions, covering 171 different, and forming 188 cohorts. To date, NRDRS complete the initial stage of resources buildup.Nex stage will be focused on clinical research and clinical trials related to rare diseases based on NRDRS. This article is on the process of building NRDRS, the potential support for conducting clinical research and clinical trials related to rare diseases, and the challenges will be faced.

Phenotype and genetic studies of the cases with ATXN2 intermediate-length CAG-repeat expansion in spinocerebellar ataxia type 2 pedigree / 中华神经科杂志

Objective:To explore the phenotype and molecular genetic features of spinocerebellar ataxia type 2 (SCA2) cases with ATXN2 intermediate-length CAG-repeat expansion.Methods:Fragment analysis by capillary electrophoresis was performed to detect the dynamic mutations in the samples of the probands in 1 383 pedigrees with autosomal dominant inherited ataxia in Research Center for Motor Disorders and Neurogenetic Diseases, Department of Neurology, China-Japan Friendship Hospital from 2005 to 2018. The clinical and genetic features of individuals carrying the ATXN2 intermediate-length CAG-repeat expansion were carefully analyzed.Results:Two hundred and three individuals (including the probands and members of their families) in 163 families carried the expanded CAG repeats in ATXN2 gene, among which 107 individuals in 93 families carried the intermediate-length CAG-repeats. Within 20 parent-child pairs, the CAG repeats increased 0-28 copies in 16 pairs with paternal inheritance, and 0-4 copies in 4 pairs with maternal inheritance.Conclusions:For suspected SCA2 cases, ATXN2 gene testing should be performed on the parental members and adult offspring members in the family. Dynamic mutations testing is essential to identify the individuals with ATXN2 intermediate-length repeat expansion, which is very important for genetic counseling.

Phenotype analysis of the families with Gerstmann-Str?ussler-Scheinker syndrome caused by prion protein gene mutations / 中华神经科杂志

Objective:To explore the clinical, imaging features and pathogenic mutations in three cases of Gerstmann-Str?ussler-Scheinker syndrome (GSS) with ataxia.Methods:Since 2014, totally 137 probands with autosomal dominant or sporadic ataxia were treated in the Department of Neurology, China-Japan Friendship Hospital. They were screened for mutations in prion protein (PRNP) gene using next-generation sequencing. Spinocerebellar ataxia 1, 2, 3, 6, 7, 8, 12, 17 and dentatorubral-pallidoluysian atrophy were excluded by capillary electrophoresis. Potential pathogenic variants were confirmed by Sanger sequencing. Pathogenicity assessment was interpreted according to the American College of Medical Genetics standards and guidelines. Clinical phenotypes and imaging features of patients were analyzed in detail.Results:Three pedigrees of GSS caused by PRNP gene variants were found. The probands of three pedigrees carried reported heterozygous missense mutation c.305C>T (p.P102L), all onset in adults. All of the three probands showed walking instability and dysarthria, additionally, the proband of pedigree 1 showed parkinsonian signs, the proband of pedigree 2 had cognitive impairment. Brain magnetic resonance imaging showed cerebellar atrophy of different degrees in probands 2 and 3, while pallidum hyperintense signal in proband 1.Conclusions:GSS as a rare subtype of prion disease, could be characterized by cerebellar ataxia. For patients with ataxia, attention should be paid to GSS disease-causing gene mutations in genetic testing. Early diagnosis based on genetic testing will be instrumental in genetic counseling and birth defect intervention in pedigree members.

Phenotype analysis of patients of spinocerebellar ataxia with trinucleotide repeat expansion of ATXN8OS gene / 中华神经科杂志

Objective:To investigate the clinical and genetic characteristics of patients with CTA/CTG trinucleotide repeat expansion of ATXN8OS gene.Methods:The CTA/CTG trinucleotide repeats of ATXN8OS gene were detected in 1 689 spinocerebellar ataxia cases from Research Center for Movement Disorders and Neurogenetics, Department of Neurology, China-Japan Friendship Hospital in 2005—2017. The correlation between clinical phenotypes and expanded CTA/CTG repeats in the ATXN8OS gene of patients was studied carefully, and compared with 100 healthy controls.Results:Twenty-one patients with pathological CTA/CTG repeat expansion of ATXN8OS gene were collected. Eighteen of them carried the alleles with more than 80 repeats, whose common initial symptom was gait instability, followed by dysarthria and dysphagia with disease progression. Four of the 18 patients presented with head or truncal tremor. The other three patients carried the alleles with the repeats ranging from 70 to 79, whose initial symptom was walking instability, gradually appeared dysarthria, with no dysphagia or tremor. The repeat lengths ranged from 19 to 42 in the 100 healthy controls. The brain magnatic resonance imaging of almost all the patients showed moderate to severe cerebellar atrophy, and some patients with mild atrophy of the brainstem except one case with corpus callosum dysplasia.Conclusions:Most of the patients with CTA/CTG repeat expansion presented with ataxia and dysarthria. Brain magnetic resonance imaging showed significant cerebellar atrophy, suggesting that the mutation is related to SCA8 gene.

Clinical phenotypes study of autosomal recessive cerebellar ataxia type 1 caused by SYNE 1 gene mutations / 中华神经科杂志

Objective@#To investigate the clinical features of autosomal recessive cerebellar ataxia type 1 (ARCA1) and analyze the pathogenic variants in SYNE 1 gene.@*Methods@#A cohort of 80 probands of autosomal recessive cerebellar ataxia pedigrees excluding Friedreich ataxia were detected by whole-exome sequencing technology. Potential pathogenic variants were confirmed by Sanger sequencing. Clinical phenotypes of positive patients were analyzed in detail.@*Results@#Three pedigrees of ARCA1 caused by SYNE 1 gene variants were found. The proband of pedigree 1 carried homozygous frameshift mutation c.12670dupC(p.L4224fs), presented as pure cerebellar ataxia. The proband of pedigree 2 carried compound heterozygous mutations c.20826+1G>T and c.25954C>T(p.R8652X), presented as cerebellar ataxia plus upper motor neuron dysfunction. The proband of pedigree 3 carried compound heterozygous mutations c.21955C>T(p.Q7319X) and c.23777C>A(p.T7926K), presented as mental behavior and cognitive impairment, cerebellar ataxia and upper motor neuron dysfunction. Brain MRI showed obvious cerebellar atrophy in all patients, and the fronto-temporal lobes were also found slight atrophy in proband of pedigree 3.@*Conclusions@#The phenotype of ARCA1 caused by SYNE 1 gene mutations is characterized by cerebellar ataxia, maybe accompanied with motor neuron damage and cognitive dysfunction. ARCA1 is a rare form of autosomal recessive cerebellar ataxia in Chinese population, with a complex phenotype. The use of next generation sequencing allows the rapid analysis of ARCA1, and will likely further expand genotype-phenotype correlations.

Clinical phenotypes study of autosomal recessive cerebellar ataxia type 1 caused by SYNE 1 gene mutations / 中华神经科杂志

Objective To investigate the clinical features of autosomal recessive cerebellar ataxia type 1 (ARCA1) and analyze the pathogenic variants in SYNE 1 gene. Methods A cohort of 80 probands of autosomal recessive cerebellar ataxia pedigrees excluding Friedreich ataxia were detected by whole?exome sequencing technology. Potential pathogenic variants were confirmed by Sanger sequencing. Clinical phenotypes of positive patients were analyzed in detail. Results Three pedigrees of ARCA1 caused by SYNE 1 gene variants were found. The proband of pedigree 1 carried homozygous frameshift mutation c.12670dupC(p.L4224fs), presented as pure cerebellar ataxia. The proband of pedigree 2 carried compound heterozygous mutations c. 20826+1G>T and c. 25954C>T(p. R8652X), presented as cerebellar ataxia plus upper motor neuron dysfunction. The proband of pedigree 3 carried compound heterozygous mutations c.21955C>T(p.Q7319X) and c.23777C>A(p.T7926K), presented as mental behavior and cognitive impairment, cerebellar ataxia and upper motor neuron dysfunction. Brain MRI showed obvious cerebellar atrophy in all patients, and the fronto?temporal lobes were also found slight atrophy in proband of pedigree 3. Conclusions The phenotype of ARCA1 caused by SYNE 1 gene mutations is characterized by cerebellar ataxia, maybe accompanied with motor neuron damage and cognitive dysfunction. ARCA1 is a rare form of autosomal recessive cerebellar ataxia in Chinese population, with a complex phenotype. The use of next generation sequencing allows the rapid analysis of ARCA1, and will likely further expand genotype?phenotype correlations.

The clinical, imaging, intestinal pathological characteristics of gluten ataxia: a case report in Chinese mainland / 中华神经科杂志

Objective To investigate the clinical,imaging,intestinal pathological characteristics and prognosis of gluten ataxia (GA).Methods The clinical data,treatment and prognosis in a patient with GA that was confirmed by pathology and hospitalized in the Department of Neurology,China-Japan Friendship Hospital in July 2018,were analyzed retrospectively.The related literature was reviewed and the clinical feature was summarized.Results The patient is a 41-year old man.He suffered from progressive cerebellar ataxia,and the brain magnetic resonance imaging exhibited diffused cerebellar atrophy.Serum human leukocyte antigen (HLA) tests showed that the patient carried HLA-DQ2 genotype.IgA type anti-gliadin antibody was positive (39.39 RU/ml).Duodenoscopy biopsy revealed mild villus atrophy and lymphocytic infiltration,indicating celiac disease.The diagnosis of GA was established then and the patient was administered gluten-free diet combined with intravenous immunoglobulin,which markedly improved the cerebellar symptoms and signs of cerebellar speech,walk capability and daily living activities.He could do long distance driving independently two months later.Conclusions GA is one of immune-mediated reversible acquired cerebellar ataxia caused by gluten sensitivity.The genotype,serologic features,and clinical phenotype of GA in Chinese mainland population might be similar with those in European and American countries.

Discussion on the standard of clinical genetic testing report and the consensus of gene testing industry / 中华医学遗传学杂志

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

Boucher-Neuh(a)user syndrome caused by compound heterozygous mutations: a case report and literature review / 中华神经科杂志

Objective To investigate the clinical manifestations, genetic basis and related literatures of Boucher-Neuh(a)user syndrome(BNS), hoping to help physicians recognize this rare disease. Methods A 25-year-old BNS patient was reported.The clinical manifestations and the laboratory data including fundus examination, blood testing, brain MRI and genetic data were summarized.The related literatures were also reviewed.Results The patient presented with tremors, ataxia, secondary sexual characteristics dysplasia,epilepsy, and then got worse progressively.Brain MRI showed severe cerebellar atrophy.Two mutations of PNPLA6 gene were found: one is the heterozygous mutation c.1811C >T (p.A604V),which has not been reported;another is c.2990C>T(p.S997L),which has been reported as a pathogenic mutation related to BNS.Conclusion PNPLA6-related BNS may be considered for adolescent patients with tremor and ataxia,secondary sexual characteristics dysplasia and epilepsy.

Clinical value of serum CA125 and HE4 combined with vaginal color Doppler in early screening of ovarian cancer among high-risk populations / 重庆医学

Objective To explore the clinical value of serum CA125 and HE4 combined with transvaginal color Doppler(TVCD)examination in early screening of ovarian cancer among high-risk populations.Methods The included research subjects were divided into 3 groups:100 cases in the healthy group,80 cases in the high-risk group and 32 cases in the ovarian cancer group.The serum CA125 and HE4 levels and ultrasonic scores were compared among 3 groups.Results The HE4 and CA125 levels and ultrasound scores in the ovarian cancer group were significantly increased compared with the other two groups,the difference was statistically significant(P＜0.01);the positive detection rate of CA125 plus HE4 levels combined with ultrasonic examination in the high-risk group was higher than that of other detection method(P＜0.05);the sensitivity and specificity of CA125+HE4 combined with vaginal ultrasound screening were obviously higher than those of other screening method,the difference was statistically significant(P＜0.05);the specificity of HE4 was significantly higher than that of CA125,but its sensitivity was lower than that of CA125(P＜0.05).Conclusion CA125 and HE4 combined with TVCD is helpful for early screening of ovarian cancer in high-risk populations,easy to save medical cost and improves its detection rate.

Plasma vitamin E and coenzyme Q10 levels and clinical significance in patients with autosomal recessive cerebellar ataxia / 中华神经科杂志

Objective To analyze plasma vitamin E and CoQ10 levels in patients with autosomal recessive cerebellar ataxia for finding the evidence of the related pathogenesis research and therapeutic strategies.Methods The plasma vitamin E and CoQ10 levels were detected by high performance liquid chromatography (HPLC) with diode array detector in 123 probands of autosomal recessive cerebellar ataxia pedigrees.Quantitation was performed using vitamin E and CoQ10 external standard and two 5-point calibration curve;clinical manifestations were analyzed simuhaneously.Results Vitamin E and CoQ10 levels of healthy subjects in the plasma were (8.77 ± 2.28) μg/ml and (1.31 ± 0.38) μg/ml,respectively;the plasma vitamin E and CoQ10 levels of patients were (5.61 ± 2.04) μg/ml and (0.79 ± 0.26) μg/ml,respectively,which were significantly lower than those in healthy controls (t =11.87,13.15;all P＜ 0.01).Clinical manifestations were characterized by cerebellar symptoms,and gait instability was usually the first recognized abnormality.Most of early onset occurred before the age of 25 years (111/123);dysarthria and abnormal eye movement were observed,with cerebellar atrophy on MRI;concomitant symptoms were also present.Conclusions HPLC analysis shows that the plasma vitamin E and CoQ10 levels of patients with autosomal recessive cerebellar ataxia are generally lower than those in the healthy controls.Several patients with significant reductions in these two levels have genetic defects.The combination of clinical phenotypes,biochemical indexes and genetic analyses will be helpful for the establishment of diagnosis and specific treatment.

Homozygosity mapping and mutation analysis of a consanguineous marriage family with autosomal recessive cerebellar ataxia / 中华神经科杂志

Objective To identify the pathogenic gene for a Chinese Han consanguineous marriage family with autosomal recessive cerebellar ataxia by homozygosity mapping and mutation analysis.Methods Six members of the family were enrolled in this study,including 3 patients,the unaffected sibling and their parents of first cousin marriage.After excluding GAA repeats mutation of FXN gene,whole-genome single nucleotide polymorphism (SNP) microarray scanning and homozygosity mapping were performed to localize the candidate gene.The coding regions and intronic flanking sequences of the candidate genes were analyzed.Results Four candidate regions were identified,including 2p25.3,9q22.2-34.3,13q12.3-14.3 and 17p13.The SETX gene localizing in 9q22.2-34.3 that is responsible for ataxia with oculomotor apraxia 2 was analyzed at first.There were 4 mutations in exon 10,including three missense mutations (c.3576T ＞ G,p.D1192E ; c.3754G ＞ A,p.G1252R; c.4156A ＞ G,p.I1386V) and a deletion mutation (c.5084_5087delAGTC,p.Q1695_S1696del).Three patients were homozygous of the 4 mutations,an unaffected sibling was normal,and their parents were heterozygous of 4 mutations.Conclusions The pathogenic haplotype comprising four mutations of the SETX gene was identified in the consanguinity family.c.5084_5087delAGTC (p.Q1695_S1696del) is a novel mutation.The affected individuals of this family were characterized by mild phenotype and slow progress without oculomotor apraxia,indicating the clinical variability of the disease.

Clinical analysis of different methods in the treatment of severe in peri-menopausal syndrome in 216 case / 中国综合临床

Objective To observe the effective treatment of severe in peri-menopausal syndrome,and improve the quality of life of women in perimenopausall and postmenopausal women.Methods We review the different treatment methods in the 216 patients diagnosed with moderate to severe menopausal syndrome.Group A:simple hormone replacement therapy (HT) of 60 cases.Group B:simple treatment of traditional Chinese medicine of 90 cases.Group C:hormone replacement and comprehensive therapy of Chinese medicine of 66 cases.Follow up the improvement of symptoms and adverse reactions after the treatment one and three month respectively.Results The three groups after treatment in patients with clinical symptoms were improved after three month.Efficient comparisons among third group,the differences were statistically significant (90％ (54/60),82％ (76/90),100％ (66/66);x2 =13.160,P ＜ 0.01).Adverse reactions of 3 treatment group comparison difference had statistical significance (45％ (27/60,1％ (1/90),6％ (4/66);x2 =60.720,P ＜0.01).Compared with pure hormone treatment group,treatment group of Chinese medicine,comprehensive treatment group adverse reactions happen was less,the difference was statistically significant(P＜0.01).Chinese medicine treatment group and combined treatment group,there was no statistically significant difference (P ＞0.05).Conclusion Severe menopausal syndrome with hormone replacement therapy indications without contraindications suggestions take comprehensive treatment of traditional Chinese and Western medicine,The hormone supplement contraindications or unwilling to hormone replacement therapy,also has good effect of Chinese medicine treating.

Advance in research on spinocerebellar ataxia 17 / 中华医学遗传学杂志

Hereditary spinocerebellar ataxia type 17 (SCA17) is an autosomal dominantly inherited progressive degenerative disease of the nervous system. Also known as Huntington's disease-like 4(HDL4), SCA17 mainly features ataxia, muscle dystonia and psychiatric symptoms. The gene predisposing to SCA17 has been mapped and cloned, which encodes a TATA-binding protein (TBP). A CAG repeat expansion in the coding region of TBP gene can cause polyglutamine chain extension in the protein. This paper reviews recent progress in the research on SCA17 in regard to its clinical, etiology, pathology and pathogenesis.

Clinical and genetic study of spinocerebellar ataxias 3 within a consanguinity family / 中华神经科杂志

Objective To investigate the inheritance principle of the expanded GAG repeat allele and the clinical features of spinocerebellar ataxias 3 (SCA3) in a consanguinity family with first cousin marriage.Methods The CAG repeats of SCA3 gene were amplified by means of polymerase chain reaction.Fragment analysis with laser-induced fluorescence in capillary electrophoresis were performed for the positive samples detected by agarose gel electrophoresis.Furthermore,the clinical features were analyzed carefully.Results Fragment analysis revealed that the proband carried 2 alleles with 56 and 72 CAG repeats separately.The proband' s father carried 28 and 66,and the expanded CAG repeat allele inherited from his grandfather.The proband' s mother carried 33 and 56,and the expanded CAG repeat allele inherited from his grandmother.The proband' s son carried 27 and 85 and presented with dystonia besides ataxia.Conclusions The proband' s parents have the common ancestors.Their alleles with expanded CAG repeats probably come from the same allele of their ancestor.The GAG repeat is more unstable in the paternal inheritance than in the maternal inheritance.The 71-year-old asymptomatic family member carry the allele with 56 CAG repeats,which indicates the 56 CAG repeats may be not associated with the disease.The patients within this family have variable clinical features,especially the juvenile-onset case presents with apparent dystonia.

Molecular and clinical study of spinocerebellar ataxia type 17 / 中华神经科杂志

Objective To investigate the clinical features and genetic mutations of spinocerebellar ataxia type 17 (SCA17).Methods The pathological CAG triplet repeat expansions of the SCA3,SCA1,SCA2,SCA6,SCA7,SCA8,SCA12,SCA17 and dentatorubral pallidoluysian atrophy genes were analyzed in 708 probands of autosomal dominant familial SCA and 1 19 sporadic SCA cases.The CAG repeats of TATA-binding protein (TBP) gene were amplified by means of polymerase chain reaction and agarose gel electrophoresis.For the samples with two alleles,fragment analysis based on CEQ8000 sequencer was applied to analyze the CAG repeat numbers.Furthermore,the correlation between clinical features and CAG repeat in the TBP gene was studied carefully.Results The expanded CAG repeats in the TBP gene was detected in 5 cases with 37/50,36/45,38/52,38/53,36/54 separately.And the main clinical manifestations were ataxia and memory impairment.Conclusion These findings indicate that SCA17 might be a rare subtype of SCA in the Chinese population and the clinical features of SCA17 cover a wider spectrum than previously reviewed.

Mutation of mitochondrial transfer RNA for leucine 1 causing variable mitochondrial diseases / 中华神经科杂志

Objective Mitochondrial transfer RNA for leucine 1(MTTL1)is one of the most important causative genes of oxidative phosphorylation disorders.To understand the clinical,pathological and molecular genetics features of the disordel's caused by MTTL1 mutation.18 patients with a causative mutation in MTTL1 were analyzed.Methods The clinical features,the findings of tlleir biochemistry tests.the neuroimagings,the pathology of biopsied muscles and hereditary characteristics were retrospectively summarized.Results The mutations mt3243A>G and mt3271A>T within MTTL1 gene led to variant syndrome,encephalomyopathies with lactic acidosis and stroke like episodes,diabetes mellitus,progressive external ophthalmoplegia,leish syndrome and complex mitochondrial syndrome were reported.Usually,most patients were sporadic but maternal transmission was the common inherited model.Conclusion The disorders caused by the MTTL1 mutation are hishly phenotypic vailable.There is no association between phenotype and heteroplasmy in muscle.

Clinical variability of Charcot-Marie-Tooth disease type 1A patients with PMP22 duplication mutation / 中华神经科杂志

Objective To investigate the characteristics of PMP22 duplication mutation and the clinical variability of Charcot-Marie-Tooth disease type 1A (CMT1A) patients. Methods PMP22 duplication mutation analysis were performed in 45 cases diagnosed probably CMT by combination of improved allele-specific PCR-restriction enzyme digestion and short tandem repeat (STR) analysis based on laser-induced fluorescence detection in capillary electrophoresis. The clinical features of the positive cases were precisely analyzed. Results With the combined use of two methods, PMP22 duplication was detected in 21 cases, i.e. 10 CMT1 cases with typical presentations including weakness and atrophy in the distal limbs, and 11 atypical cases with special phenotypes including 1 case with mild dizziness, 1 case with hearing loss, 2 cases with recurrent limbs weakness, 2 cases with postural tremor in the upper limbs, 4 cases with cerebellar ataxia and 1 case with epilepsy. Conclusions The improved allele-specific PCR-restriction enzyme digestion provides the accurate, reliable and feasible method to detect PMP22 duplication, which is the most common cause of CMT. Comprehensive analysis of clinical, electrophysiological and pathological features of the CMT1A patients with positive PMP22 duplication indicate the high clinical variability of this disease.

Clinical and neuroimaging features of 143 patients with multiple system atrophy / 中华神经科杂志

Objective To study the clinical and neuroimaging features of subtypes of multiple system atrophy (MSA) and their correlations. Methods One hundred and forty-three MSA cases fulfilled Gilman diagnostic criteria (1999) were recruited and their clinical subtypes and stages were classified. Using the staging methods of the pontine cross sign and putaminal slit proposed by Horimoto, 108 patients showed abnormalities in MRI and were further evaluated. The relationship between the subtypes of MSA, disease duration, and MRI abnormalities has been analyzed. Results Of 143 MSA patients, the male-to-female ratio is 1.3:1 ; 93 cases are diagnosed with MSA-C, 39 with MSA-P, and 11 with MSA-P + C; 90 cases with probable diagnosis, and 53 with possible diagnosis. Of the 76 MSA-C cases with MRI abnormalities, 36 (47%) show the pontine cross sign and 10 (13%) show the putaminal slit; of the 24 MSA-P cases with MRI abnormalities, 6 (25%) show the pontine cross sign and 6 (25%) show theputaminal slit. In addition, MSA-C cases with shorter disease duration demonstrate earlier stages of the pontine cross sign. Conclusions In this study, the number of MSA-C cases is more than MSA-P, which might be related to the ethnic background. In neuroimaging, both the pontine cross sign and the putaminal slit are the marked features of MSA. To some degree, the subtypes of MSA are related with the features of imaging, that is, MSA-C patients present the pontine cross sign more often than MSA-P, and the putaminal slit is a comparatively common feature among MSA-P cases.

Prenatal diagnosis of spinocerebellar ataxia type 3 based on umbilical cord blood and short tandem repeat analysis / 中华神经科杂志

Objective To investigate methods for prenatal diagnosis of spinocerebellar ataxia type 3 (SCA3).Methods Cordocentesis were performed in the pregnant SCA3 female proband of pedigree during the 20th gestational week.Polymerase chain reaction (PCR) and short tandem repeat (STR) analysis based on CEQS000 sequencer were applied to analyze the CAG repeat of SCA3 gene.Results The proband had 31/75 CAG repeat alleles of SCA3 gene; her spouse had 14/27 CAG repeat alleles; the fetuse had 14/31 CAG repeat alleles (14 repeat from the father,and 31 repeat from the mother),which is in conformity with Medelian inheritance.The fetuse inherited the normal CAG repeat allele from the mother.The above results of the fetuse were verified after its birth.Conclusion Detecting CAG repeat dynamic mutation of SCA3 gene based on umbilical cord blood and STR analysis could be a rapid and reliable method for prenatal diagnosis of SCA3.