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Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781294


OBJECTIVE@#To explore the genetic basis of a child with idiopathic mental retardation.@*METHODS@#Clinical data and peripheral blood sample of the child were collected. Genomic DNA was extracted and subjected to copy number analysis using single nucleotide polymrophism array comparative genome hybridization (SNP-aCGH) and targeted capture and next generation sequencing (NGS).@*RESULTS@#No microdeletion/microduplication were detected by SNP-aCGH. NGS has detected homozygous c.722delA (p.Asp241fs) variant of the LISN1 gene, which is known to underlie autosomal recessive mental retardation-27 (MRT 27). Both parents are carriers of the variant, conforming to the autosomal recessive inheritance.@*CONCLUSION@#A novel pathogenic variant of the LINS1 gene has been identified, which probably underlies the MRT 27 in the patient.

Criança , Hibridização Genômica Comparativa , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Humanos , Deficiência Intelectual , Genética , Proteínas , Genética
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763677


BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) is high, though its severity is often underestimated. Our aim is to provide an estimate of the prevalence of severe NAFLD in T2DM and identify its major predictors. METHODS: T2DM patients (n=328) not previously known to have NAFLD underwent clinical assessment, transient elastography with measure of liver stiffness (LS) and controlled attenuation parameter (CAP), and genotyping for patatin like phospholipase domain containing 3 (PNPLA3) and 17β-hydroxysteroid-dehydrogenase type 13 (HSD17B13). RESULTS: Median LS was 6.1 kPa (4.9 to 8.6). More than one-fourth patients had advanced liver disease, defined as LS ≥7.9 kPa (n=94/238, 29%), and had a higher body mass index (BMI) than those with a LS <7.9 kPa. Carriage of the G allele in the PNPLA3 gene was associated with higher LS, being 5.9 kPa (4.7 to 7.7) in C/C homozygotes, 6.1 kPa (5.2 to 8.7) in C/G heterozygotes, and 6.8 kPa (5.8 to 9.2) in G/G homozygotes (P=0.01). This trend was absent in patients with ≥1 mutated HSD17B13 allele. In a multiple linear regression model, BMI and PNPLA3 genotype predicted LS, while age, gender, disease duration, and glycosylated hemoglobin did not fit into the model. None of these variables was confirmed to be predictive among carriers of at least one HSD17B13 mutated allele. There was no association between CAP and polymorphisms of PNPLA3 or HSD17B13. CONCLUSION: Advanced NAFLD is common among T2DM patients. LS is predicted by both BMI and PNPLA3 polymorphism, the effect of the latter being modulated by mutated HSD17B13.

Alelos , Índice de Massa Corporal , Diabetes Mellitus , Diabetes Mellitus Tipo 2 , Técnicas de Imagem por Elasticidade , Fibrose , Genótipo , Hemoglobina A Glicada , Heterozigoto , Homozigoto , Humanos , Modelos Lineares , Fígado , Hepatopatias , Hepatopatia Gordurosa não Alcoólica , Fosfolipases , Prevalência
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776798


OBJECTIVE@#To explore clinical and genetic features of a pedigree affected with autosomal recessive neuromyotonia and axonal neuropathy (NMAN).@*METHODS@#For the proband and her parents, clinical data was collected, genomic DNA was extracted from peripheral blood samples. Triplet primed-PCR was carried out to detect dynamic mutation of DMPK and ZNF9 genes, which are responsible for myotonic dystrophy, by capillary electrophoresis. High-throughput sequencing was used to screen variants of candidate genes for Mendelian disorders involving the nervous system. Candidate variants were confirmed by Sanger sequencing. The genotype of the variant was determined in the parents and 100 healthy controls. Pathogenicity of the variant was assessed by ACMG criterion.@*RESULTS@#Mutation of DMPK and ZNF9 genes was excluded. DNA sequencing has identified a homozygous missense variant (c.335C>T, p.R119W) in the HINT1 gene. Both parents were found to carry the variant. The same variant was not found among the healthy controls. According to the ACMG criterion, the missense variant was classified as a pathogenic variant.@*CONCLUSION@#The c.335C>T (p.R119W) of the HINT1 gene probably underlie the disease in this pedigree. Above finding provided further evidence for the connection between HINT1 and NMAN and enriched the mutation spectrum of HINT1 gene.

Feminino , Genótipo , Homozigoto , Humanos , Síndrome de Isaacs , Genética , Proteínas do Tecido Nervoso , Genética , Linhagem
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776768


OBJECTIVE@#To explore the genetic basis of a patient with early-onset Parkinson disease from a consanguineous family.@*METHODS@#Homozygosity mapping and Sanger sequencing of cDNA were used to identify the causative mutation.@*RESULTS@#A homozygous missense variation (c.56C>G, p.Thr19Arg) in the PARK7 gene was identified in the patient. In silico analysis suggested the c.56C>G variation to be pathogenic.@*CONCLUSION@#Homozygous c.56C>G variation of the PARK7 gene was the disease-causing variation in this family.

Consanguinidade , Homozigoto , Humanos , Mutação de Sentido Incorreto , Doença de Parkinson , Genética , Linhagem , Proteína Desglicase DJ-1 , Genética
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-775792


OBJECTIVE@#To explore the molecular basis for an individual with postnatal deafness and provide genetic counseling for her family.@*METHODS@#Following extraction of genomic DNA from peripheral blood samples, 127 genes associated with deafness were subjected to targeted capturing and next generation sequencing. Suspected mutation was verified by Sanger sequencing.@*RESULTS@#The proband was found to carry a homozygous c.1893C>A mutation in the TECTA gene, which is located in the tectorial membrane of inner ear and may cause premature termination of translation of TECTA protein. In addition, two heterozygous mutations, c.13010C>T and c.12790G>A, were found in the USH2A gene. Whilst the former is likely to be pathogenic, the latter has unknown clinical significance. Further analysis suggested that all three mutations have derived from the parents of the proband.@*CONCLUSION@#The homozygous c.1893C>A mutation of the TECTA gene probably underlies the proband's hearing loss which conformed to an autosomal recessive inheritance.

Surdez , Proteínas da Matriz Extracelular , Genética , Feminino , Proteínas Ligadas por GPI , Genética , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Humanos , Mutação , Linhagem
Journal of Experimental Hematology ; (6): 1580-1584, 2019.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-775682


OBJECTIVE@#To analyze the hematological characteristics of HbE homozygotes.@*METHODS@#Complete blood cells count and hemoglobin electrophoresis were used for phenotypic analysis of 78 cases with HbE homozygotes from Yunnan province, China. The PCR-fluorescence hybridization was used to detect the common gene mutation of thalassemia. The hematological indexes, including MCV, MCH, Hb, HbA2, HbF and HbE were statistically analyzed between groups with different sex, ages and compound α thalassemia status.@*RESULTS@#In HbE homozygotes (HbEE), 89.5% (17/19) children presented mild to moderate microcytic hypochromic anemia, and 10.5% of them presented moderate anemia. 39.6% (19/48) of women with HbEE developed mild anemia ,while 11 cases of male with HbE homozygotes were asymptomatic. The levels of MCV and MCH in HbE homozygotes increased by co-inheritance of α thalassemia mutation.@*CONCLUSION@#The clinical phenotype of HbE homozygote shows highly heterogeneous, which is relates with age, sex and co-inheriting α-globin genotypes. In Hb EE women and children are more likely to develop mild to moderate anemia. The microcytic hypochromic anemia degree is relieved when HbEE combined with α- thalassemia.

Criança , China , Feminino , Genótipo , Hemoglobina E , Genética , Homozigoto , Humanos , Masculino , Fenótipo , Talassemia alfa
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781323


OBJECTIVE@#To explore the feasibility of high performance liquid chromatography (DHPLC) combined with multiple ligation-dependent probe amplification (MLPA) for the prenatal diagnosis of spinal muscular atrophy (SMA).@*METHODS@#Three families who had given birth to children with SMA type I were subjected to prenatal diagnosis. Peripheral blood samples were collected from the three couples, and 10 mL amniotic fluid was taken for each fetus through amniocentesis at 16-24 gestational week. Following DNA extraction, maternal contamination was excluded by STR analysis. Copy numbers of the SMN genes were detected by denaturing high performance liquid chromatography (DHPLC). Relative copy number of SMN1, SMN2 and reference genes was detected with a MLPA P021 assay kit.@*RESULTS@#The three couples were all found to harbor heterozygous deletion of exon 7 of the SMN1 gene by DHPLC. MLPA analysis also suggested that the three couples were all carriers of SMA mutations. The fetus of family 1 harbored homozygous deletion of exons 7 and 8 of the SMN1 gene, in addition with heterozygous deletion of exons 7 and 8 of the SMN2 gene, suggesting that the fetus had SMA. The fetus of family 2 also harbored homozygous deletion of exons 7 and 8 of the SMN1 gene, while the copy number of SMN2 gene was normal, suggesting that the fetus was a SMA patient too. The fetus of family 3 harbored heterozygous deletion of exons 7 and 8 of the SMN1 gene, in addition with heterozygous deletion of exons 7 and 8 of the SMN2 gene, suggesting that the fetus was a carrier.@*CONCLUSION@#DHPLC can effectively screen carriers of SMA mutations. Combined DHPLC and MLPA can provide accurate diagnosis for fetuses with a high risk for SMA.

Criança , Cromatografia Líquida de Alta Pressão , Feminino , Homozigoto , Humanos , Atrofia Muscular Espinal , Diagnóstico , Técnicas de Amplificação de Ácido Nucleico , Gravidez , Diagnóstico Pré-Natal , Deleção de Sequência , Proteína 1 de Sobrevivência do Neurônio Motor , Genética , Proteína 2 de Sobrevivência do Neurônio Motor , Genética
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771864


OBJECTIVE@#To investigate the gene mutations types and the clinical characteristics in 3 patients with hereditary coagulation factor Ⅶ deficiency.@*METHODS@#The phenotype diagnosis was validated by detecting the coagulation parameters including prothrombin time (PT),activated partial thromboplastin time (APTT), fibrinogen (FIB), FⅦ activity (FⅦ: C) and specific antigens (FⅦ: Ag) of proband and its family members. All exons, exon-intron boundaries, 5' untranslated regions and 3' untranslated regions of F7 gene were amplified with PCR. Potential mutations were detected by direct sequencing of purified PCR products. Suspected mutations were confirmed by sequencing of the opposite strand.@*RESULTS@#A total of 5 different mutations were identified in 3 patients with hereditary coagulation factor Ⅶ deficiency and family members, including 4 misssense mutations and 1 splice site mutation. Out of 3 cases of hereditary coagulation factor Ⅶ deficiency 2 had double heterozygous mutation, I had homozygous mutations. Patient 1 had p.His408Gln with p.Arg413Gln double heterozygous mutations, her sister had p.His408Gln with p.Arg413Gln double heterozygous mutations, another one had p.His408Gln mono-heterozygous mutation, their correspo FⅦ: C were 5%, 3%, 75%. Patient 2 had p.Arg364Gln with p.His408Gln double heterozygous mutations, her brother had p.Arg364Gln with IVS6-1G>A double heterozygous mutations, their corresponding FⅦ: C were 2.0%, 2.0%. Patient 3 had p.Arg337Cys homozygous mutation, FⅦ: C was 3.0%.@*CONCLUSION@#A total of 5 different mutations were identified in 3 patients with hereditary coagulation factor Ⅶ deficiency, the p.His408Gln is a common mutation, the FⅦ: C and FⅦ: Ag have no correlation with clinical phenotypes.

Fator VII , Deficiência do Fator VII , Feminino , Heterozigoto , Homozigoto , Humanos , Masculino , Mutação , Linhagem , Fenótipo
Electron. j. biotechnol ; 31: 1-9, Jan. 2018. ilus, graf, tab
Artigo em Inglês | LILACS (Américas) | ID: biblio-1022023


Background: Lettuce is a globally important leafy vegetable and a model plant for biotechnology due to its adaptability to tissue culture and stable genetic transformation. Lettuce is also crucial for functional genomics research in the Asteraceae which includes species of great agronomical importance. The development of transgenic events implies the production of a large number of shoots that must be differentiated between transgenic and non-transgenic through the activity of the selective agent, being kanamycin the most popular. Results: In this work we adjusted the selection conditions of transgenic seedlings to avoid any escapes, finding that threshold concentration of kanamycin was 75 mg/L. To monitor the selection system, we studied the morphological response of transgenic and non-transgenic seedlings in presence of kanamycin to look for a visual morphological marker. Several traits like shoot length, primary root length, number of leaves, fresh weight, and appearance of the aerial part and development of lateral roots were affected in non-transgenic seedlings after 30 d of culture in selective media. However, only lateral root development showed an early, qualitative and reliable association with nptII presence, as corroborated by PCR detection. Applied in successive transgenic progenies, this method of selection combined with morphological follow-up allowed selecting the homozygous presence of nptII gene in 100% of the analyzed plants from T2 to T5. Conclusions: This protocol allows a simplified scaling-up of the production of multiple homozygous transgenic progeny lines in the early generations avoiding expensive and time-consuming molecular assays.

Plantas Geneticamente Modificadas/genética , Alface/genética , Seleção Genética , Canamicina/análise , Reação em Cadeia da Polimerase , Alface/química , Plântula , Homozigoto
Yonsei Medical Journal ; : 801-805, 2018.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-716421


Cerebral amyloid angiopathy (CAA) is associated with perivascular disruption, which is caused by progressive amyloid-beta (Aβ) deposition in vessels. Previous autopsy studies have shown that the prevalence of CAA in Alzheimer's disease (AD) is 70% to 90%. CAA is principally characterized by restricted lobar microbleeds (MBs), which can be detected by gradient-echo T2* (GRE) and susceptibility-weighted imaging (SWI). We herein report on a 62-year-old man who presented with 8 years of memory impairment. The apolipoprotein E (APOE) genotype was ε4/ε4, and a brain GRE performed 28 months before death revealed mild atrophy and no MBs. At autopsy, the patient scored “A3, B3, C3” according to the National Institute on Aging-Alzheimer's Association guidelines; the patient thus exhibited a high level of AD neuropathological changes. Furthermore, immunohistochemical staining for Aβ showed antibody accumulation and severe cerebral amyloid angiopathic changes in numerous vessels with amyloid deposits. Our case suggests that radiological CAA markers, such as cerebral microbleed (CMB) or cerebral superficial siderosis, may not suffice to detect amyloid angiopathy in cerebral vessels. CAA should therefore be considered as a combined pathology in APOE ε4 homozygotes with AD, even if such patients do not exhibit CMB on MRI.

Doença de Alzheimer , Amiloide , Apolipoproteínas , Apolipoproteínas E , Atrofia , Autopsia , Encéfalo , Angiopatia Amiloide Cerebral , Genótipo , Homozigoto , Humanos , Imagem por Ressonância Magnética , Memória , Pessoa de Meia-Idade , Patologia , Placa Amiloide , Prevalência , Siderose
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-741682


BACKGROUND/OBJECTIVES: This study aimed to test the association between APOA5 3'-UTR variants (rs662799) and cardiometabolic traits in Koreans. SUBJECTS/METHODS: For this study, epidemiological data, Apolipoprotein A5 (APOA5) genotype information, and lymphoblastoid cell line (LCL) biospecimens from a subset of the Ansung-Ansan cohort within the Korean Genome and Epidemiology study (KoGES-ASAS; n = 7,704) as well as epidemiological data along with genomic DNA biospecimens of participants from a subset of the Korea National Health and Nutrition Examination Survey (KNHANES 2011-12; n = 2,235) were obtained. APOA5 mRNA expression was also measured. RESULTS: APOA5 rs662799 genotype distributions in both the KoGES-ASAS and KNHANES groups were 50.6% for TT, 41.3% for TC, and 8.1% for CC, which are similar to those in previous reports. In both groups, minor C allele carriers, particularly subjects with CC homozygosity, had lower high-density lipoprotein (HDL) cholesterol and higher triglyceride levels than TT homozygotes. Linear regression analysis showed that the minor C allele significantly contributed to reduction of circulating HDL cholesterol levels [β = −2.048, P < 0.001; β = −2.199, P < 0.001] as well as elevation of circulating triglyceride levels [β = 0.053, P < 0.001; β = 0.066, P < 0.001] in both the KoGES-ASAS and KNHANES groups. In addition, higher expression levels of APOA5 in LCLs of 64 healthy individuals were negatively associated with body mass index (r = −0.277, P = 0.027) and circulating triglyceride level (r = −0.340, P = 0.006) but not significantly correlated with circulating HDL cholesterol level. On the other hand, we observed no significant difference in the mRNA level of APOA5 according to APOA5 rs662799 polymorphisms. CONCLUSIONS: The C allele of APOA5 rs662799 was found to be significantly associated with cardiometabolic traits in a large Korean population from the KoGES-ASAS and KNHANES. The effect of this genotype may be associated with post-transcriptional regulation, which deserves further experimental confirmation.

Alelos , Apolipoproteínas , Grupo com Ancestrais do Continente Asiático , Índice de Massa Corporal , Linhagem Celular , Colesterol , HDL-Colesterol , Estudos de Coortes , DNA , Estudos Epidemiológicos , Epidemiologia , Genoma , Genótipo , Mãos , Homozigoto , Humanos , Coreia (Geográfico) , Modelos Lineares , Lipoproteínas , Inquéritos Nutricionais , RNA Mensageiro , Triglicerídeos
Psychiatry Investigation ; : 306-312, 2018.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-713458


OBJECTIVE: The therapeutic effect of methylphenidate (MPH) in treating attention-deficit/hyperactivity disorder (ADHD) has been related to the alpha-2A adrenergic receptor (ADRA2A) gene -1291C/G single nucleotide polymorphism (SNP). We investigated the effect of MPH in treating Taiwanese children and adolescent with ADHD and its relation to the ADRA2A gene -1291C/G SNP. METHODS: The subjects with DSM-IV ADHD diagnosis underwent a titration period to find out the dose of MPH for maintenance treatment. After 4 weeks maintenance treatment, the effect of MPH was evaluated by the Swanson, Nolan and Pelham version IV total scores. The subjects with more than 25% score reduction were referred to responders and those with ≥50% improvement were considered as better responders. The -1291C/G variant of the ADRA2A gene was identified by DNA sequencing and what relevance it has to the MPH response was examined by binary logistic regression analysis. RESULTS: Of the 59 subjects, 44 (74.6%) were responsive to MPH treatment and the responsiveness was not shown to be associated with the ADRA2A gene -1291C/G SNP. As the responsive subjects were categorized as moderate responders and better responders and subjected to statistical analysis, the GG homozygotes showed a greater chance to have a better response to MPH treatment than CC homozygotes (p=0.02), with an odds ratio of 32.14 (95% CI=1.64–627.80). CONCLUSION: The ADRA2A gene -1291C/G SNP is associated with the efficacy of MPH for the treatment of ADHD in Taiwanese children and adolescents. The responsive subjects bearing homozygous -1291G allele are more likely to have a better response to MPH treatment.

Adolescente , Alelos , Criança , Diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Homozigoto , Humanos , Modelos Logísticos , Metilfenidato , Razão de Chances , Farmacogenética , Polimorfismo de Nucleotídeo Único , Receptores Adrenérgicos alfa 2 , Análise de Sequência de DNA
Med. UIS ; 30(3): 31-38, sep.-dic. 2017. tab, graf
Artigo em Espanhol | LILACS (Américas) | ID: biblio-894215


Resumen Introducción: La enfermedad de Parkinson se caracteriza por la degeneración y pérdida de las neuronas dopaminérgicas en el cerebro. Existen factores genéticos involucrados en su desarrollo, en su forma de inicio temprano como el gen PARK2, codificante de la parkina, una E3 ubiquitín ligasa, lo que hace que en caso de mutaciones pierda su capacidad reguladora de degradación de proteínas causando estrés y muerte celular. Objetivo: Determinar la presencia de cambios moleculares en los exones 3, 4, y 5 de PARK2 en un grupo de 29 pacientes y 21 controles colombianos con enfermedad de Parkinson de inicio temprano o con antecedentes familiares de ella y la posible correlación con las manifestaciones clínicas de los pacientes. Materiales y métodos: Estudio descriptivo observacional (entre junio de 2013 y noviembre de 2014) en donde se realizó extracción de ADN de sangre total y se utilizó la técnica de PCR para cada uno de los exones. Finalmente se procedió a la secuenciación automática, análisis de las secuencias con el software Sequencher y comparación con información de bases de datos. Resultados: Se identificó una variante en estado homocigoto (Ala46Thr) en el exón 4 en un paciente no reportada anteriormente, posiblemente no patogénica y la variante Ser167Asn en estado heterocigoto en el mismo exón en otro paciente, considerada patogénica y reportada con anterioridad en poblaciones asiática y europea. No se identificaron variantes en los controles. Conclusiones: Los cambios no descritos antes en la población colombiana, -Ala46Thr y Ser167Asn-, fueron identificados en el grupo de pacientes. MÉD.UIS. 2017;30(3):31-8.

Abstract Introduction: Parkinson's disease is characterized by the degeneration and loss of dopaminergic neurons in the brain. There are genetic factors involved in its development in its early onset form, such as the PARK2 gene encoding the parkin, an E3 ubiquitin ligase, which in the case of mutations loses its ability to regulate protein degradation causing stress and cell death. Objective: To determine the presence of molecular changes in PARK2 exons 3, 4 and 5 in a group of 29 patients and 21 colombian controls with early onset Parkinson's disease or a family history of Parkinson's disease and the possible correlation with clinical manifestations from the patients. Materials and methods: Observational descriptive study (between june of 2013 and november of 2014) where DNA extraction of whole blood was performed and the PCR technique was used for each of the exons. Finally, we proceeded to the automatic sequencing, analysis of the sequences with the Sequencher software and comparison with information of databases. Results: A homozygous variant (Ala46Thr) in exon 4 was identified in one patient not previously reported, possibly nonpathogenic and the Ser167Asn variant in heterozygous state in the same exon in another patient, considered pathogenic and previously reported in populations Asian and European. No variants were identified in the controls. Conclusions: changes not previously described in the colombian population, -Ala46Thr and Ser167Asn-, were identified in the group of patients and not in the controls. MÉD.UIS. 2017;30(3):31-8.

Humanos , Masculino , Feminino , Adulto , Doença de Parkinson , Proteínas Associadas à Doença de Parkinson , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Mutação com Perda de Função , Genes , Homozigoto , Mutação
National Journal of Andrology ; (12): 1121-1126, 2017.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-812822


Objective@#To assess the association of the FSHR Thr307Ala-Asn680Ser gene polymorphism with male infertility.@*METHODS@#We searched Pubmed, EMBASE, Web of Science, CNKI, and WANFANG databases for literature on the correlation of the FSHR Thr307Ala-Asn680Ser gene polymorphism with male infertility published from 2005 to the present time. According to the inclusion criteria, we included 12 epidemiological case-control studies and subjected them to a comprehensive analysis with the Stata11.0 software.@*RESULTS@#A total of 2 893 male infertility patients and 3 312 controls were involved in the 12 studies. The Thr307Ala (rs6165) gene polymorphism was shown to be a risk factor for male infertility among the three comparison models (homozygous comparison model, hybrid comparison model and dominant comparison model), with the pooled odds ratios (OR) of 1.26 (95% CI: 1.03-1.54, P = 0.023), 1.18 (95% CI: 1.03-1.36, P = 0.018), and 1.20 (95% CI: 1.05-1.37, P = 0.006), respectively. And the Asn680Ser(rs6166) polymorphism was a risk factor for male infertility in the homozygous comparison and recessive comparison models, with the pooled ORs of 1.24, (95% CI: 1.05-1.45, P = 0.009) and 1.20 (95% CI: 1.04-1.39, P = 0.013), respectively. Layered meta-analysis showed that in the homozygous comparison model, the Thr307Ala-Asn680Ser polymorphism is a risk factor for male infertility in the white population, with the OR of 1.37 (95% CI: 1.03-1.82, P = 0.003) and 1.21 (95% CI: 1.00-1.47, P = 0.048), respectively.@*CONCLUSIONS@#In the homozygous model (GG vs AA), the FSHRThr307Ala-Asn680Ser gene polymorphism might be a protective factor against male infertility.

Estudos de Casos e Controles , Hormônio Foliculoestimulante Humano , Genética , Homozigoto , Humanos , Infertilidade Masculina , Genética , Masculino , Polimorfismo Genético , Fatores de Risco
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-633540


High gravidity hydatidiform mole (HM) without normal pregnancy is very rare. The challenge of managing such cases will dwell on the concern of having normal conception versus having another molar gestation and its neoplastic sequelae. Presented in this paper is a case of a 32-year-old, gravida 5 para 0 (0040) who was admitted for the management of her fifth molar pregnancy. She underwent suction curettage and administration of methotrexate chemoprophylaxis. Genetic testing was done, which revealed a homozygous mutation in NLRP7, the gene implicated in recurrent molar gestations. This paper discusses the proper approach to determine the cause of recurrent molar pregnancies, as well as the management and prognosis of such cases.

Humanos , Feminino , Adulto , Número de Gestações , Metotrexato , Curetagem a Vácuo , Mola Hidatiforme , Homozigoto , Testes Genéticos , Mutação , Prognóstico , Quimioprevenção , Dente Molar
Bahrain Medical Bulletin. 2017; 39 (1): 33-37
em Inglês | IMEMR (Mediterrâneo Oriental) | ID: emr-185650


Background: Bone pain frequency and optimal methods of vitamin D [VD] administration in adult patients with sickle cell anemia [SCA] are unclear

Objective: To assess bone pain frequency and level of VD in adult SCA patients after vitamin D medication

Setting: Salmaniya Medical Complex, Bahrain

Design: A Prospective Controlled Trial

Method: The study was performed from 1 January 2013 to 31 December 2014. Sixty-nine SCA patients were studied and compared with an age and gender-matched control group. Bone pain frequency was assessed using Visual Analogue Scale [VAS]. Measurement of serum level of VD, parathormone [PTH], calcium and alkaline phosphatase [ALP] at baseline, one and three months after treatment. Vitamin D Deficiency [VDD] was defined as <50 nmol/L. The mean difference of biochemical and clinical parameters was compared using paired Student t-test

Result: Fifty-one [74%] patients from the study group and 14 [20.3%] patients from the control group had VDD. Twenty-six [37.7%] patients were treated with IM injection of 600,000 IU once and 25 [36.2%] were treated with oral capsule of 50,000 IU weekly. Patients on IM treatment had pain frequency of 56 episodes per month before treatment, which was reduced to 43 [P<0.05] after one month; further reduction to 34 episodes [P<0.01] was achieved after three months. Patients on oral medication had pain frequency of 57 episodes per month before treatment, which reduced to 50 episodes after one month [P<0.05] and 40 after 3 months [P<0.01]. Vitamin D level increased to 54.15 +/- 2.73 in one month compared to 19.55 +/- 9.63 nmol/ml [P<0.05] before treatment. Patients on oral medication had VD increment of 31.64 +/- 4.44 compared to 22.11 +/- 9.46 nmol/ml [P<0.05] after one month and 53.69 +/- 2.37 nmol/ml after three months [P<0.001]

Conclusion: Frequency of bone pain was reduced significantly in adult SCA patients with VDD after one month of treatment of vitamin D3 injection with normalization of serum level

Adulto , Adolescente , Feminino , Humanos , Masculino , Adulto Jovem , Colecalciferol/administração & dosagem , Anemia Falciforme/tratamento farmacológico , Homozigoto , Adulto , Dor/tratamento farmacológico , Barein
IBJ-Iranian Biomedical Journal. 2017; 21 (5): 294-302
em Inglês | IMEMR (Mediterrâneo Oriental) | ID: emr-188486


Background: Inherited retinal diseases [IRDs] are a group of genetic disorders with high degrees of clinical, genetic and allelic heterogeneity. IRDs generally show progressive retinal cell death resulting in gradual vision loss

IRDs constitute a broad spectrum of disorders including retinitis pigmentosa and Leber congenital amaurosis. In this study, we performed genotyping studies to identify the underlying mutations in three Iranian families

Methods: Having employed homozygosity mapping and Sanger sequencing, we identified the underlying mutations in the crumbs homologue 1 gene. The CRB1 protein is a part of a macromolecular complex with a vital role in retinal cell polarity, morphogenesis, and maintenance

Results: We identified a novel homozygous variant [c.1053-1061del; p.Gly352-Cys354del] in one family, a combination of a novel [c.2086T>C; p.Cys696Arg] and a known variant [c.2234C>T, p.Thr745Met] in another family and a homozygous novel variant [c.3090T>A; p.Asn!030Lys] in a third family

Conclusion: This study shows that mutations in CRB1 are relatively common in Iranian non-syndromic IRD patients

Humanos , Mutação , Retinite Pigmentosa/genética , Amaurose Congênita de Leber/genética , Mapeamento Cromossômico , Sequenciamento Completo do Genoma , Proteínas do Olho , Proteínas de Membrana , Proteínas do Tecido Nervoso , Homozigoto
Protein & Cell ; (12): 811-822, 2017.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-756922


β-Thalassemia is a global health issue, caused by mutations in the HBB gene. Among these mutations, HBB -28 (A>G) mutations is one of the three most common mutations in China and Southeast Asia patients with β-thalassemia. Correcting this mutation in human embryos may prevent the disease being passed onto future generations and cure anemia. Here we report the first study using base editor (BE) system to correct disease mutant in human embryos. Firstly, we produced a 293T cell line with an exogenous HBB -28 (A>G) mutant fragment for gRNAs and targeting efficiency evaluation. Then we collected primary skin fibroblast cells from a β-thalassemia patient with HBB -28 (A>G) homozygous mutation. Data showed that base editor could precisely correct HBB -28 (A>G) mutation in the patient's primary cells. To model homozygous mutation disease embryos, we constructed nuclear transfer embryos by fusing the lymphocyte or skin fibroblast cells with enucleated in vitro matured (IVM) oocytes. Notably, the gene correction efficiency was over 23.0% in these embryos by base editor. Although these embryos were still mosaic, the percentage of repaired blastomeres was over 20.0%. In addition, we found that base editor variants, with narrowed deamination window, could promote G-to-A conversion at HBB -28 site precisely in human embryos. Collectively, this study demonstrated the feasibility of curing genetic disease in human somatic cells and embryos by base editor system.

Desaminase APOBEC-1 , Genética , Metabolismo , Sequência de Bases , Blastômeros , Biologia Celular , Metabolismo , Sistemas CRISPR-Cas , Embrião de Mamíferos , Metabolismo , Patologia , Feminino , Fibroblastos , Metabolismo , Patologia , Edição de Genes , Métodos , Expressão Gênica , Células HEK293 , Heterozigoto , Homozigoto , Humanos , Mutação Puntual , Cultura Primária de Células , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Globinas beta , Genética , Metabolismo , Talassemia beta , Genética , Metabolismo , Patologia , Terapêutica
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-335120


<p><b>OBJECTIVE</b>To detect pathogenic mutation of the SLC39A4 gene in a male patient with acrodermatitis enteropathica (AE).</p><p><b>METHODS</b>Peripheral venous blood sample and clinical data from the patient and his parents were collected. One hundred unrelated healthy individuals were recruited as controls. All coding exons and flanking exon-intron sequences of the SLC39A4 gene were analyzed by PCR and direct sequencing.</p><p><b>RESULTS</b>The results revealed that the patient and his mother have both carried a novel frame-shift mutation c.1110InsG (p.Gly370GlyfsX47 to TGA) in exon 6. A novel nonsense mutation c.958C to T (p.Q320X) in exon 5 was also detected in the patient and his father and grandmother. This novel mutation was not detected in the unaffected family members and 100 unrelated healthy controls.</p><p><b>CONCLUSION</b>The novel frame-shift mutation c.1110InsG (p.Gly370GlyfsX47 to TGA) derived from the mother and nonsense mutation c.958C to T (p.Q320X) of the SLC39A4 gene derived from the father may underlie the disease in the patient.</p>

Acrodermatite , Genética , Adolescente , Sequência de Bases , Proteínas de Transporte de Cátions , Genética , Éxons , Homozigoto , Humanos , Masculino , Dados de Sequência Molecular , Mutação , Linhagem , Zinco
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-72418


BACKGROUND: The interaction between killer immunoglobulin-like receptors (KIRs) and HLA class I regulates natural killer (NK) cell cytotoxicity and function. The impact of NK cell alloreactivity through KIR in liver transplantation remains unelucidated. Since the frequency of HLA-C and KIR genotypes show ethnic differences, we assessed the impact of HLA-C, KIR genotype, or KIR-ligand mismatch on the allograft outcome of Korean liver allografts. METHODS: One hundred eighty-two living donor liver transplant patients were studied. Thirty-five patients (19.2%) had biopsy-confirmed acute rejection (AR), and eighteen (9.9%) had graft failure. The HLA-C compatibility, KIR genotypes, ligand-ligand, and KIR-ligand matching was retrospectively investigated for association with allograft outcomes. RESULTS: Homozygous C1 ligands were predominant in both patients and donors, and frequency of the HLA-C2 allele in Koreans was lower than that in other ethnic groups. Despite the significantly lower frequency of the HLA-C2 genotype in Koreans, donors with at least one HLA-C2 allele showed higher rates of AR than donors with no HLA-C2 alleles (29.2% vs 15.7%, P=0.0423). Although KIR genotypes also showed ethnic differences, KIR genotypes and the number of activating KIR/inhibitory KIR were not associated with the allograft outcome. KIR-ligand mismatch was expected in 31.6% of Korean liver transplants and had no impact on AR or graft survival. CONCLUSIONS: This study could not confirm the clinical impact of KIR genotypes and KIR-ligand mismatch. However, we demonstrated that the presence of HLA-C2 allele in the donor influenced AR of Korean liver allografts.

Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Genótipo , Rejeição de Enxerto , Sobrevivência de Enxerto , Antígenos HLA-C/genética , Homozigoto , Humanos , Células Matadoras Naturais/citologia , Ligantes , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Receptores KIR/química , República da Coreia , Doadores de Tecidos , Transplante Homólogo