Hereditary hemorrhagic telangiectasia complicated by aortic sinus aneurysm caused by a pathogenic mutation in the ACVRL1 gene: a family survey / 中华皮肤科杂志

Objective:To investigate clinical and genetic characteristics of a family with hereditary hemorrhagic telangiectasia complicated by aortic sinus aneurysm, and to analyze causative genes.Methods:Clinical data and peripheral blood samples were collected from the proband and her relatives, and genomic DNA was extracted. Causative genes were screened by whole-exome sequencing, and then verified by Sanger sequencing.Results:A heterozygous mutation c.137G>A was identified at position 137 in exon 3 of the ACVRL1 gene in the proband, her daughter, grandson and granddaughter, which led to the substitution of cysteine by tyrosine at amino acid position 46 (p.C46Y) . The mutation was not found in any of the other 5 family members without clinical symptoms.Conclusion:A causative mutation c.137G>A (p.C46Y) in the ACVRL1 gene was identified in the family with hereditary hemorrhagic telangiectasia type 2 complicated by aortic sinus aneurysm, which had not been previously reported in Asian populations.

Study on mitochondrial DNA mutation in patients with primary multiple myeloma / 白血病·淋巴瘤

Objective To study the mitochondrial DNA mutation in patients with primary multiple myeloma. Methods The mitochondrial DNA of 5 patients with primary multiple myeloma in the First Hospital of Qinhuangdao from February to June 2017 were amplified by polymerase chain reaction (PCR) and sequenced directly, and the results were compared with revised Cambridge Reference Sequence (rCRS) and Human Mitochondrial Gene Database (mtDB) database. Results There were 42 mutation genes, with 52.38％(22/42) mutation genes in D-loop region, 9.52％(4/42) mutation genes in ND4L region, 2.38％(1/42) mutation genes in ND5 region, 26.19％ (11/42) mutation genes in Cytb region, 7.14％ (3/42) mutation genes in ND1 region, and 4.76％ (2/42) mutation genes in COⅡ region. Conclusion There is a high mitochondrial DNA mutation rate in patients with primary multiple myeloma.

Mitochondrial damage and related ocular disorders / 中华实验眼科杂志

Mitochondria are recognized to function as the powerhouse of the cell.The etiology of many common ocular disorders is increasingly recognized to involve either an accumulation of mitochondrial DNA (mtDNA) mutations and/or secondary mitochondrial damage.Novel pathogenic mtDNA mutations continue to be detected for primary mitochondrial ophthalmologic disorders that commonly affect the optic nerve,retina,and extraocular muscles.Mitochondrial dysfunction is also increasingly implicated in common ophthalmologic disorders,including diabetic retinopathy,age-related macular degeneration (AMD),and glaucoma.As the promise of personalized genomic medicine is becoming a reality,effective therapies for mitochondrial disorders are beginning to translate from bench to bedside along the paths of neuroprotection,gene replacement and stem cell-based regenerative paradigms.Additionally,preventing the transmission of pathogenic mtDNA mutations from mother to child is now a reality with in vitro fertilization mitochondrial replacement techniques.

Analysis of mitochondrial DNA mutation in leukemia / 肿瘤研究与临床

Objective To study the mitochondrial DNA mutation in leukemia.Methods Mitochondrial DNA of 16 leukemia patients in First Hospital of Qinhuangdao from February to June 2017 were amplified and sequenced by using polymerase chain reaction (PCR).The result was compared with revised Cambridge reference sequence (rCRS) and human mitochondrial genome database (mtDB),and the mutation was also analyzed.Results There were 106 mutation genes in total,including 47.17 ％ (50/106) in D-loop region,2.83 ％ (3/106) in ND4 region,17.92 ％ (19/106) in ND5 region,22.64 ％ (24/106) in Cytb region,7.55 ％ (8/106) in ND1 region,1.89 ％ (2/106) in Co Ⅱ region.Conclusion There is a high mitochondrial DNA mutation rate in leukemia patients.

Leigh Syndrome in Childhood: Neurologic Progression and Functional Outcome

BACKGROUND AND PURPOSE: Few studies have analyzed the clinical course and functional outcome in Leigh syndrome (LS). The aim of this study was to determine the clinical, radiological, biochemical, and genetic features of patients with LS, and identify prognostic indicators of the disease progression and neurological outcome. METHODS: Thirty-nine patients who had been diagnosed with LS at the Seoul National University Children's Hospital were included. Their medical records, neuroimaging findings, and histological/biochemical findings of skeletal muscle specimens were reviewed. Targeted sequencing of mitochondrial DNA was performed based on mitochondrial respiratory chain (MRC) enzyme defects. RESULTS: Isolated complex I deficiency was the most frequently observed MRC defect (in 42% of 38 investigated patients). Mitochondrial DNA mutations were identified in 11 patients, of which 81.8% were MT-ND genes. The clinical outcome varied widely, from independent daily activity to severe disability. Poor functional outcomes and neurological deterioration were significantly associated with early onset (before an age of 1 year) and the presence of other lesions additional to basal ganglia involvement in the initial neuroimaging. CONCLUSIONS: The neurological severity and outcome of LS may vary widely and be better than those predicted based on previous studies. We suggest that age at onset and initial neuroimaging findings are prognostic indicators in LS.

Hepatitis B virus (HBV) gene mutations related to entecavir-resistance in patients with chronic HBV infections / 中华临床感染病杂志

Objective To investigate hepatitis B virus (HBV) gene mutations related to entecavir (ETV)-resistance in patients with chronic HBV infections.Methods Serum samples were collected from 44 patients with chronic HBV infections and resistant to ETV treatment who were admitted in Ningbo No.2 Hospital during February 2010 and May 2014.The HBV polymerase regions were amplified by real-time fluorescent quantitative polymerase chain reaction (PCR) method,and the PCR products were analyzed with direct sequencing.SPSS 16.0 was used to assess the frequency of HBV polymerase gene mutations,and its relation to the viral genotype and clinical features.Results The most common HBV polymerase gene mutation was rtS202G/I (52.28％,23/44),followed by rtT184A/G/I/S (36.36％,16/44) and rtM250V/L (11.36％,5/44).Nine mutation patterns were detected,in which rtL180 + rtM204V + rtS202G/I (38.64％,17/44) and rtL180 +rtM204V + rtT184A/G/I/S (27.27％,12/44) were the most frequent ones.The difference in gene mutations between genotype B and C was of statistical significance (x2=12.294,P ＜0.01).Patients carrying rtT184A/G/I/S mutations were associated with worse liver function (x2 =14.499,P ＜ 0.01),and those carrying rtM250V/L mutations were associated with lower HBeAg positive rate (x2 =10.057,P ＜ 0.01).Conclusions rtL180M + rtM204V + rtS202G/I is the most common HBV polymerase gene mutation related to ETV resistance in patients with chronic HBV infections.Different gene mutations may be associated with HBV genotypes,severity of liver damages,and HBeAg positive rate.

A peep into mitochondrial disorder: multifaceted from mitochondrial DNA mutations to nuclear gene modulation

Mitochondrial genome is responsible for multiple human diseases in a maternal inherited pattern, yet phenotypes of patients in a same pedigree frequently vary largely. Genes involving in epigenetic modification, RNA processing, and other biological pathways, rather than "threshold effect" and environmental factors, provide more specific explanation to the aberrant phenotype. Thus, the double hit theory, mutations both in mitochondrial DNA and modifying genes aggravating the symptom, throws new light on mitochondrial dysfunction processes. In addition, mitochondrial retrograde signaling pathway that leads to reconfiguration of cell metabolism to adapt defects in mitochondria may as well play an active role. Here we review selected examples of modifier genes and mitochondrial retrograde signaling in mitochondrial disorders, which refine our understanding and will guide the rational design of clinical therapies.

Progress in mechanism of CYP4V2 gene mutations for Bietti crystalline corneoretinal dystrophy / 中华实验眼科杂志

Bietti crystalline corneoretinal dystrophy (BCD) is a common form of hereditary retinal degeneration in Chinese.Mutation of the cytochrome P450 4V2 (CYP4V2) gene,a novel family member of the cytochrome P450 genes on chromosome 4q35,has been identified in BCD patients,with the common mutation locus at c.802-8 _ 810dell7insGC (Exon7del),c.992A ＞ C (p.H331 P) and c.1091-2A ＞ G (Exon 9del).CYP4V2 is responsible for oxidation of various substrates in the metabolic pathway,especially ω-hydroxylase activity towards ω-3 polyunsaturated fatty acids (PUFAs).CYP4V2 appears to be the only CYP4 memeber at significant levels in retinal cells,and it may be a prominent contributor to local metabolism of PUFAs,mainly DHA (C22:6n-3),in retinal cells.To understand and investigate the main mechanism of CYP4V2 gene mutation causing BCD is important in the study of genetic diagnosis and genetic management of BCD.This review summarized the current advance in the genetic mechanism of BCD and function of CYP4V2 gene,elucidated the substrate specificity and unraveled the biochemical pathways that may impact function of CYP4V2 in BCD patients.

Study progress in the relationship of CYP1B1 gene mutation with primary open angle glaucoma / 中华实验眼科杂志

Primary glaucoma is a group of blinding eye diseases,including of primary open angle glaucoma (POAG),primary angle-closure glaucoma (PACG) and primary congenital glaucoma (PCG).It is thought that the pathogenesis of primary glaucoma is a comprehensive action of genetic factor,environment factor and life style,and the genetic factor plays an important role.CYP1B1 gene was firstly identified as a causal gene for PCG in 1997.After that,thousands of reports on the pathogenesis of POAG focused on CYP1B1 gene mutation.With the developing of research,researches found that CYP1B1 gene to be one of the candidate genes of POAG.The structure and function of CYP1B1 gene,the relationship between CYP1B1 and POAG were reviewed.

Estudo da Beta-catenina em tumores adrenocorticais humanos / Study of beta-catenin in human adrenocortical tumors

Introdução: A incidência de tumores adrenocorticais em crianças é particularmente elevada nas regiões sudeste e sul do Brasil, correlacionandose com a ocorrência da mutação germinativa p.R337H do supressor tumoral p53, entretanto, o carcinoma adrenocortical é uma neoplasia endócrina maligna rara em todo o mundo com uma incidência aproximada de 0,5 - 2 casos por milhão por ano. Esta condição é uma doença heterogênea, apresentando frequentemente comportamento clínico agressivo e letal. A cascata de sinalização Wnt é uma via importante de transdução de sinal em cânceres humanos e tem sido implicada na tumorigênese adrenocortical. A atividade desta via de sinalização é dependente da quantidade de beta-catenina citoplasmática e nuclear. Mutações ativadoras no gene da beta-catenina (CTNNB1) foram relatadas em diversas neoplasias humanas. Estudos demonstraram que mutações no gene CTNNB1 são os defeitos genéticos mais frequentemente encontrados em adenomas e em carcinomas adrenocorticais. O estudo destas mutações demonstrou que as alterações no gene CTNNB1 localizam-se principalmente exon 3, que codifica a porção amino terminal da beta- catenina. Objetivos: determinar a ocorrência e a frequência das mutações somáticas no exon 3 do gene CTNNB1. Adicionalmente, determinar a imunorreatividade de beta-catenina e de p53 em tumores adrenocorticais benignos e malignos de crianças e adultos. Correlacionar os resultados da análise de mutações gênicas e os dados de imunorreatividade com as características hormonais, a mutação p.R337H do p53, o diagnóstico histológico e a evolução dos tumores adrenocorticais de crianças e adultos. Métodos: Neste estudo, a análise de imunohistoquímica para beta-catenina e p53 foi realizada em 103 tumores adrenocorticais benignos e malignos (40 crianças e 63 adultos), estando as amostras histológicas alocadas em micromatriz tecidual (TMA). A pesquisa de mutações no exon 3 do gene CTNNB1 foi determinada por seqüenciamento automático em 64 tumores...

Introduction: The incidence of adrenocortical tumors in children is particularly high in the southeastern and southern regions of Brazil, correlating with the occurrence of p.R337H p53 tumor suppressor germline mutation. However, adrenocortical carcinoma is a worldwide rare endocrine malignancy with an approximate incidence of 0.5 to 2 cases per million per year. This condition is a heterogeneous disease and is often lethal. The Wnt signaling pathway is an important signal transduction pathway in human cancers and has been implicated in adrenocortical tumorigenesis. The activity of this signaling pathway is dependent on the amount of nuclear and cytoplasmic beta-catenin. Activating mutations of ?-catenin (CTNNB1) gene have been reported in several human malignancies. Studies have shown that CTNNB1 mutations are the most common genetic defect found in adrenocortical adenomas and carcinomas. The study of these mutations demonstrated that the changes in CTNNB1 gene are mainly located in exon 3, which encodes the amino terminal portion of the beta- catenin. Objectives: to determine the occurrence and frequency of CTNNB1 somatic mutations and the abnormal beta-catenin and p53 accumulation in benign and malignant adrenocortical tumors in both children and adults. We also evaluated the correlation of the gene mutations analysis and immunohistochemistry data with the hormonal characteristics, the p.R337H germline mutation, the histological diagnosis and the prognosis of adrenocortical tumors in children and adults. Methods: In this study, immunohistochemistry for beta-catenin and p53 was performed in 103 benign and malignant (40 children and 63 adults) adrenocortical tumors. The histological samples were allocated in a tissue microarray (TMA). The study of the CTNNB1 gene was performed by direct sequencing of 64 adrenocortical tumors. Results: The beta-catenin abnormal accumulation was similar in benign and malignant adrenocortical tumors of children and adults (15...(au)

K-ras gene mutation status in 454 Chinese patients with colorectal cancer / 肿瘤

Objective: To analyze the mutation status of K-ras gene in CRC (colorectal cancer) tissues and plasma samples of CRC patients, ultimately to promote the targeted agents against EGFR (epidermal growth factor receptor) (such as cetuximab and panitumumab, etc.) used in personalized treatment for CRC patients. Methods: The sequence of K-ras gene at specific sites was investigated in 431 CRC tissues and 23 plasma samples collected from 454 CRC patients, respectively. To improve the detection sensitivity, a combinatory approach was chosen which included the COLD-PCR (coamplification at lower denaturation temperature PCR) method, followed by DNA sequencing. Chi-square test was employed to analyze K-ras mutation frequencies in various sample types or subgroups of CRC patients according to age, and the difference was considered statistically significant if P value was less than 0.05. Results: The overall K-ras mutation rate was 25.29% in 431 CRC tissue samples. The two major forms of K-ras mutation were Gl 2D (mutation of glycine to an aspartate residue at codon 12) and Gl 3D (mutation of glycine to an aspartate residue at codon 13), and their occurrence frequencies were 12.99% and 6.26%, respectively. Interestingly, the overall K-ras mutation rate was 21.74% in blood samples from additional 23 CRC patients, without a significant difference from the mutation rate in the tumor samples (P > 0.05). Moreover, the occurrence frequency of anyone form of K-ras mutation was 37.94% in CRC patients aged 60 and over, which was significantly higher than the detection rate (7.30%) of the patients under the age of 60 (P < 0.01). Conclusion: COLD-PCR amplification combined with DNA sequencing method can be used to detect the mutation status of K-ras gene, and plasma samples can be used insteadly if CRC tumor tissues are unavailable. In addition, for elderly patients aged of 60 and over, it is suggested that K-ras mutation status should be routinely detected before treatment. Copyright © 2013 by TUMOR.

Detection of epidermal growth factor receptor mutations in small specimens of non-small cell lung cancer by amplification refractory mutation system / 肿瘤

Objective: To explore the feasibility of the application of small specimens as alternatives of gross specimens to detect EGFR (epidermal growth factor receptor) mutation in NSCLC (non-small cell lung cancer) by ARMS (amplification refractory mutation system). Methods: Biopsy specimens from 181 cases of NSCLC were collected, in which 157 were small specimens (including specimens acquired through CT-guided percutaneous lung biopsy, endobronchial ultrasound-guided transbronchial needle aspiration, lymph node biopsy, bronchoscopic biopsy and aspiration of pleural effusion) and 24 were gross specimens. QIAGEN DNA extraction kit was used to extract DNAs from NSCLC specimens. Then AmoyDx EGFR Mutation Test Kit - a highly sensitive real-time PCR-based test was used to detect EGFR mutations. The detection rates of EGFR mutations in small specimens and gross specimens were compared by Chi-square test or Fisher's exact test. Results: The total EGFR mutation detection rate of all biopsy specimens was 39.8% (72/181). The detection rates of small specimens and gross specimens were 38.9% and 45.8%, respectively (P = 0.515). Furthermore, EGFR mutation frequencies were significantly higher in non-smokers (P = 0.033) and in patients with adenocarcinoma (P < 0.001). Conclusion: A relatively high detection rate of EGFR mutation in NSCLC small specimens can be obtained through ARMS. For patients with advanced NSCLC whose gross specimens cannot be easily obtained, the alternative small specimens can be used in clinical EGFR mutation detection. Copyright © 2012 by TUMOR.

Mitochondrial molecular genetics for a pedigree with Leber hereditary optic neuropathy / 中华实验眼科杂志

Background Leber hereditary optic neuropathy (LHON)is a mitochondrial DNA (mtDNA)hereditary disease,so it is significant to understand the influence of DNA mutation on the occurrence of LHON.Objective This survey was to evaluate the role of mtDNA mutation in the development of LHON.Methods This survey study was approved by the Ethic Committee of Wuhan General Hospital of Guangzhou Military Command and written informed consent was obtained from each subject before the relative medial examination.Seventy-two matrilineal relatives from a family with LHON were collected for a pedigree analysis and mutation screening.Regular eye examination was performed on 11 patients,13 mutant gene carriers and 49 individuals with normal phenotype,and the degree of visual damage was graded as follows: ＞0.3 was normal,0.1-0.3 was mild damage,＜0.05-0.1 was moderate damage,＜0.02-0.05 was severe damage and ＜0.01 was very severe damage.Clinical characteristics of LHON was evaluated.The periphery blood sample of 2-4 ml was collected from individuals to separate the mononuclear cells,and the mtDNA was extracted by modified high salt method.MtDNA was amplified by PCR and the mutation loci was sequenced.Results PCR amplification product sequencing of mutant gene showed that both G11778A and T14502C mutations were detected in 24 of 72 matrilineal relatives,but only 11 of 24 carriers developed LHON.No abnormal clinical findings were seen in the 13 carriers,showing a less 50％ penetrance in this family.There was no G11778A or/and T14502C mutation in the normal phenotype individuals of this family.The onset age for vision impairment in 11 affected matrilineal relatives varied from 8 to 50 years old,with the mean age of 24.36 years old,showing a significantly lower age than that of the 13 carriers (5-72 years old,mean 40.38 years old) (t =2.102,P=0.049).Conclusions This study suggests that the Gl1778A and T14502C mutation in mitochondrial DNA is one of causes in the development of LHON.The primary G11778A mutation together with T14502C mutation in mtDNA is a factor for the occurrence of LHON,hut it is not sufficient to the development of LHON.An effective “second hit” process will play an inducing role for LHON.

Identifying potential pitfalls in interpreting mitochondrial DNA mutations of male infertility cases.

Background & objectives: Recently, a significantly higher ratio of nucleotide changes in the mtDNA genes: COII, ATPase 6, ATPase 8, ND2, ND3, ND4, and ND5 was reported in spermatozoa from populations of infertile Indian men, compared suggesting that screening for mtDNA mutations could provide insight into the aetiology of male infertility. In this study, we examined the published data and found serious errors in the original acquisition and analysis of the data. Methods: The mtDNA data associated with male infertility in Indian populations were retrieved from the published sources. The mtDNA substitution values of infertile and control groups were evaluated using phylogenetic methods and previously published mtDNA phylogenies. Results: Most of the mtDNA polymorphisms reported as significantly correlated with infertility were more commonly found in general populations. Further, our analysis showed that some of the mtDNA substitutions were erroneously overestimated in the infertile groups and underestimated in the control groups, and vice-versa. Interpretation & conclusions: Contrary to earlier claims, our analysis demonstrated no significant association between the mtDNA polymorphisms and male infertility in these studies. Further, these errors in the published data impune the usefulness of mitochondrial molecular analyses in male infertility diagnosis.

Application of DNA microarray in the identification of Candida spp. and mutations of ERG11 gene resulting in fluconazole resistance / 中华皮肤科杂志

Objective To investigate the performance of DNA microarray in identifying 6 common Candida spp. and validating ERG11 mutations resulting in fluconazolc-resistance in Candida albicans. Methods Oligonucleotide probes were designed and synthesized targeting the species-specific sequence in the internal transcribed spacer 2 (ITS2) region of rDNA of Candida albicans, Candida tropicalis, Candida glabrata, Candida dubliniensis, Candida parapsilosis and Candida krusei, as well as 6 sequences embracing the following mutations respectively in ERG11 gene leading to fluconazole-resistance, i.c., T541C, A 1090G, C1361T, G1537A, G1547A, and T1559C, then arranged onto a chip. Twelve 50-base-pair oligonucleotides were artificially synthesized based on the above specific sequences, and utilized to hybridize with the DNA microarray. Thirty-lbur Candida strains, including 29 C. albicans, 1 Candida tropicalis, 1 Candida glabrata,1 Candida dubliniensis, 1 Candida parapsilosis and 1 Candida krusei, were detected with microarray. Genomic DNA was extracted from these tested strains and underwent multiple PCR for the amplification of ITS2 region and ERGI 1 gene. Sequencing was performed to analyze the sequence of ERG11 in 29 strains of C. albicans and the results were compared with those of DNA microarray hybridization. Results Multiple PCR successfully produced ITS2 fragment of 307-415 bp from all the 34 strains, as well as ERG11 fragment of 1712 bp from 29 C. albicans strains. DNA microarray hybridization offered the same results in species identification of the 34 strains with their given information, as well as in mutation detection of the 29 strains of C. albicans with ERG11 sequencing results. Also, the 6 synthesized oligonucleotides containing the muta- tions were identified precisely as T541C, A1090G, C1361T, G1537A, G1547A, and T1559C, and the 6 species specific oligonucleotieds were identified correctly as C. albicans, C. tropicalis, C. glabrata, C. dubliniensis, C. parapsilosis and C. krusei Both the sensitivity and the specificity of the microarray were 100%. Conclu- sion DNA microarray is a quite reliable method to identify Candida spp. and fluconazole resistance-associ- ated mutations in the ERG11 gene of C. albicans.

Clinical characteristics of diabetic pedigree with mtDNA 12026A→G mutation in Nd4 region / 中国糖尿病杂志

Objective To investigate clinical traits of 2 families members habouring mtDNA 12026A→G mutation based on our previous studies.Methods 25 members in 2 families with probands with mtDNA 12026 mutation were examined.All their clinical and biochemical data were collected.Total genome was extracted conventionally from peripheral leucocytes of all participants,and PCR-RFLP techniques were applied to screen A to G substitution at nucleotide 12026 of mtDNA in ND4 region.Results We found 13 individuals habouring the 12026 A→G mutation in 2 pedigrees,all without deafness.Among them,5 with diabetes were found.Interestingly,we found 3 individuals with hyperthyroidism in one family(one also combined with diabetes).Conclusions Our findings suggest that diabetic families with mtDNA 12026 A→G mutation in ND4 region can have different clinical pictures,and may involve in autoimmune diseases

Relationship between Mitochondrial DNA Point Mutation and Noise-induced Sensorineural Hearing Loss / 항공우주의학회지

BACKGROUND: A different sequence change in the mitochondrial 12S rRNA gene has been proposed as a candidate mutation in the sensorineural hearing loss. The purpose of this study was to study the association between the noise-induced sensorineural hearing loss and A to G mutation at nucleotide 1555 of mitochondrial DNA. METHODS: subjects were reviewed by history and medical records, and audiological and clinical data were obtained. Blood sampling was done on 101 normal controls, 51 with noise-induced sensorineural hearing loss, and 12 with sensorineurnal deafness. The DNA of these individuals were extracted, and mitochondrial genome were analyzed by polymerase chain reaction (PCR). Subsequently, the coding sequence of mitochondrial genome was sequenced and compared to the normal sequence, and all sequence variations were analyzed by restriction endonuclease BsmA I. RESULTS: Mitochondrial DNA mutant (1555A-->G) was not detected by PCR in all Korean patients with noise-induced hearing loss, sensorineural hearing loss, and in normal controls with no hearing loss. The DNA sequencing of PCR products did not reveal an A to G substitution at nucleotide 1,555 of mitochondrial DNA. CONCLUSION: This result suggests that the noise-induced sensorineural hearing loss is not associated with mitochondrial DNA mutation (1555A-->G).

MELAS Syndrome Presenting as Occipital Brain Infarct: Case Report / 대한뇌혈관외과학회지

MELAS syndrome is characterized by mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. A 14-year-old male presented with symptoms that resemble stroke including headache, seizure, visual disturbance and slight left hemiparesis. Laboratory investigation showed elevated lactate level in the blood. Brain computed tomography and magnetic resonance image revealed acute infarction in the right occipitoparietal lobe, which was not restricted to a specific vascular territory. Magnetic resonance spectroscopy showed decreased N-acetyl aspartate and increased lactate level in the affected lobe. A molecular genetic analysis identified A3243G point mutation in the peripheral blood leukocytes and confirmed MELAS syndrome. We describe clinical, radiological and molecular genetic findings in the patient with MELAS syndrome presenting occipital brain infarct.

A Mutation in the Connexin30Gene in a Pedigree with Hidrotic Ectodermal Dysplasia / 中华皮肤科杂志

Objective To analyses the mutation of connexin30gene in a pedigree with hidrotic ec-todermal dysplasia(HED).Methods Blood samples were obtained from18affected and16normal individ-uals in this family.Mutation scanning was carried out by PCR and direct sequencing.Results A transition,at position on connexin30gene31(G→A),leading to a missense mutation(G11R),was detected in18patients,but was not found in16normal individuals in this HED family and in188unrelated,population-matched control individuals,which indicated that it did not represent common polymorphism.Conclusion A missense mutation(31G→A)in the connexin30gene has been determined in the pedigree with HED,which is probably one of the molecular bases of the pathogenesis of the disease.

Mutations in ED1 Gene of Two Pedigrees with X-linked Hypohidrotic Ectodermal Dysplasia / 中华皮肤科杂志

Objective To detect ED1 gene mutations in the families with X-linked hypohidrotic ec-todermal dysplasia (XLHED). Methods Blood samples were obtained from 2 pedigrees. All 8 exons and flanking intronic boundaries of ED1 gene were amplified with polymerase chain reaction technique and then directly sequenced. Results Two mutations were found in ED1 gene. One was splicing mutation (IVS8+5 del G), the other was missense mutation (A959G). None of the mutations was found in normal individuals of two XLHED families and in 188 unrelated, population-matched control individuals. Conclusion Out of the ED1 gene mutations identified in 2 Chinese XLHED families, IVS8+5del G is a novel mutation.