Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 51
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Yi Chuan ; 41(8): 669-676, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31447418

RESUMO

ß-thalassemia (ß-thal) is a fatal and disabling inherited blood disorder with diverse phenotypes. The same or similar genotype of ß-thal can manifest variable clinical severities. It is the hotspot and emphasis in the field of hematopathy and genetic diseases to explore genetic modifiers that influence the phenotype of ß-thal. This review illustrates the deteriorating and amelioratig modifiers from two aspects: genotypes of α-globin and quantitative trait locus of fetal hemoglobin (Hb F). Variations of transcription factors which reactive the γ-globin gene expression and ß-globin cluster cis-acting elements were introduced emphatically. Finally, clinical applications and future development prospects of ß-thal genetic modifiers are introduced by examples.


Assuntos
Talassemia beta/genética , Hemoglobina Fetal/genética , Genótipo , Humanos , Fenótipo , Fatores de Transcrição/genética , alfa-Globinas/genética , Globinas beta/genética , gama-Globinas/genética
2.
Yi Chuan ; 41(8): 716-724, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31447422

RESUMO

In order to investigate the genetic variations and the clinical manifestations of a range of congenital ectrodactyly family and to summarize the split hand/foot malformation (SHFM) types and their related pathogenic genes, we conducted phenotypic analyses of patient's limbs by physical and X-ray examination. The haplotypes were analyzed by using the extracted genes from peripheral blood on D10S1709, D10S192, D10S597, D10S1693 and D10S587 loci, and the mutation duplication loci were confirmed by Array-CGH detection. The pathogenic factors and inheritance pattern of SHFM were analyzed based on family investigation and gene analysis. Results demonstrate the proband's phenotype is typically of a congenital SHFM which is manifested by missing bilateral index and middle fingers, short bilateral thumbs, deformed left ring finger with webbing of the skin missing at the middle finger; bilateral big toe with the second and the third toe missing, fourth and fifth toe fusion leading to a deformed toe separated from the first toe by the middle of the foot. The haplotype analyses show that there is a repeat of at least 610 kb in chromosome 10q24.31-10q24.32 region. Array-CGH analysis shows 10q24.31 (102 832 650-103 511 083) ×3. Our results demonstrate that the pathogenic gene variation of ectrodactyly in this family is due to duplication of 10q24.31 (102 832 650~103 511 083). The haplotype 165-251-289-219-102 can be used as a disease marker for detecting 10q24.31~10q24.32 allele for SHFM.


Assuntos
Duplicação Cromossômica , Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/genética , Deformidades Congênitas dos Membros/genética , Cromossomos Humanos Par 10/genética , Humanos , Linhagem
3.
Yi Chuan ; 41(8): 746-753, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31447425

RESUMO

Personal genomic information benefits from accumulated big data and its application is no longer limited to scientific research. Presently, it is undergoing the transformation to daily medical practice. Systematic arrangement, archiving and rational utilization of disease-related genomic information is an important foundation of future precision medicine. Hemoglobinopathy is prevalent in southern China, but its molecular pathological basis has racial specificity. To facilitate clinical diagnosis and genetic screening of hemoglobinopathy in southern China, we established the LOVD gene data management system for the variation and phenotype spectrum of hemoglobinopathy. Then we designed an integrated and efficient on-line auxiliary accurate diagnosis and risk assessment system in order to assist clinicians to make comprehensive diagnosis and genetic counseling in a short time based on cloud standardized annotated library of specific hemoglobinopathy variants and diagnostic repository. The methodology and experience of improving the clinical decision-making efficiency of diseases with big data and artificial intelligence technology can be used as an example in the clinical and preventive application of other diseases.


Assuntos
Bases de Dados Genéticas , Sistemas de Apoio a Decisões Clínicas , Hemoglobinopatias/genética , Mutação , China , Aconselhamento Genético , Testes Genéticos , Humanos
4.
Brain ; 142(8): 2215-2229, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31199454

RESUMO

Charcot-Marie-Tooth disease is a hereditary motor and sensory neuropathy exhibiting great clinical and genetic heterogeneity. Here, the identification of two heterozygous missense mutations in the C1orf194 gene at 1p21.2-p13.2 with Charcot-Marie-Tooth disease are reported. Specifically, the p.I122N mutation was the cause of an intermediate form of Charcot-Marie-Tooth disease, and the p.K28I missense mutation predominately led to the demyelinating form. Functional studies demonstrated that the p.K28I variant significantly reduced expression of the protein, but the p.I122N variant increased. In addition, the p.I122N mutant protein exhibited the aggregation in neuroblastoma cell lines and the patient's peroneal nerve. Either gain-of-function or partial loss-of-function mutations to C1ORF194 can specify different causal mechanisms responsible for Charcot-Marie-Tooth disease with a wide range of clinical severity. Moreover, a knock-in mouse model confirmed that the C1orf194 missense mutation p.I121N led to impairments in motor and neuromuscular functions, and aberrant myelination and axonal phenotypes. The loss of normal C1ORF194 protein altered intracellular Ca2+ homeostasis and upregulated Ca2+ handling regulatory proteins. These findings describe a novel protein with vital functions in peripheral nervous systems and broaden the causes of Charcot-Marie-Tooth disease, which open new avenues for the diagnosis and treatment of related neuropathies.

5.
Yi Chuan ; 39(3): 232-240, 2017 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-28420619

RESUMO

ß-thalassemia is an autosomal recessive monogenic disease that is caused by defects in the production of ß-like globin chains. Activation of γ-globin gene and the increase in fetal hemoglobin expression have been demonstrated as one of the most important factors to ameliorate the clinical outcome of ß-thalassemia patients. In this study, 202 genes or miRNAs associated with human hemoglobin gene expression from 1802 ß-thalassemia patients were analyzed with target capture and next generation sequencing strategies in terms of functional variants that might affect hemoglobin gene expression. The subsequent bioinformatics analysis included assessments of sequence quality, the variants within the target regions and the 5'UTR with potential effects on upstream open reading frames (uORFs). Among the 41 variants in 5'UTR potentially affecting the uORFs identified in the study, two variants (chr19: 41859418 G > A and chr1:153606541 C > T) were experimentally validated with dual-luciferase assays to be capable of significantly down-regulating the expression of TGFB1 and CHTOP gene, respectively. The present study demonstrated a system suitable for evaluating the importance of variants in 5'UTRs affecting uORFs in 202 human genes associated with hemoglobin expression. Research with this approach could provide potential targets that may contribute to the clinical phenotypes and provide biomarkers for precise diagnosis of ß-thalassemia.


Assuntos
Fases de Leitura Aberta/genética , Regiões 5' não Traduzidas/genética , Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala , Humanos
6.
Clin Chem Lab Med ; 55(3): 358-367, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-27754957

RESUMO

BACKGROUND: Spinal muscular atrophy (SMA) is mainly caused by deletions in SMA-related genes. The objective of this study was to develop gene-dosage assays for diagnosing SMA. METHODS: A multiplex, quantitative PCR assay and a CNVplex assay were developed for determining the copy number of SMN1, SMN2, and NAIP. Reproducibility and specificity of the two assays were compared to a multiple ligation-dependent probe amplification (MLPA) assay. To evaluate reproducibility, 30 samples were analyzed three times using the three assays. A total of 317 samples were used to assess the specificity of the two assays. RESULTS: The multiplex quantitative PCR (qPCR) assay had higher reproducibility. Intra-assay CVs were 3.01%-8.52% and inter-assay CVs were 4.12%-6.24%. The CNVplex assay had ratios that were closer to expected (0.49-0.5 for one copy, 1.03-1.0 for two copies, and 1.50-1.50 for three copies). Diagnostic accuracy rates for the two assays were 100%. CONCLUSIONS: The multiplex qPCR assay was a simple, rapid, and cost-effective method for routine SMA diagnosis and carrier screening. The CNVplex assay could be used to detect SMAs with complicated gene structures. The assays were reliable and could be used as alternative methods for clinical diagnosis of SMA.


Assuntos
Variações do Número de Cópias de DNA/genética , Marcadores Genéticos/genética , Atrofia Muscular Espinal/diagnóstico , Proteína Inibidora de Apoptose Neuronal/genética , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Genótipo , Humanos , Reação em Cadeia da Polimerase Multiplex , Atrofia Muscular Espinal/genética , Reprodutibilidade dos Testes , Deleção de Sequência , Proteína 2 de Sobrevivência do Neurônio Motor/genética
7.
Blood Cells Mol Dis ; 55(1): 62-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25976469

RESUMO

Thalassemia is an inherited autosomal recessive blood disorder characterized by the underproduction of globin chains as a consequence of globin gene defects, resulting in malfunctioning red blood cells and oxygen transport. Analysis of globin chains is an important aspect of thalassemia research. In this study we developed a capillary zone electrophoresis (CZE) method for human globin determination in the diagnosis of thalassemia and hemoglobin variants. To demonstrate the utility of this approach, α/ß area ratios were determined for samples from 310 thalassemia patients and healthy controls. The separation was performed on uncoated capillary with simple preparation. Distinct globin peaks were resolved in 17 min, and coefficients of variation (CV) for migration time and areas ranged from 0.37%-1.69% and 0.46%-6.71%, respectively. Receiver operating characteristic (ROC) curve analysis of the α/ß area ratios gave 100% sensitivity and specificity for indicating ß-TI/TM, and 100% sensitivity and 97.4% specificity for Hb H disease. Hemoglobin G-Honolulu (Hb G-Honolulu) and Hb Westmead (Hb WS) were successfully detected using this CZE method. This automated methodology is simple, rapid and cost-effective for the fast determination of human globin chains, which could be an important diagnostic tool in the field of hemoglobinopathies.


Assuntos
Eletroforese Capilar/métodos , alfa-Globinas/isolamento & purificação , Talassemia alfa/diagnóstico , Globinas beta/isolamento & purificação , Talassemia beta/diagnóstico , Estudos de Casos e Controles , Hemoglobina H/isolamento & purificação , Hemoglobinas Anormais/isolamento & purificação , Humanos , Sensibilidade e Especificidade , Talassemia alfa/sangue , Talassemia beta/sangue
8.
BMC Musculoskelet Disord ; 16: 11, 2015 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-25888055

RESUMO

BACKGROUND: Spinal muscular atrophy (SMA) is caused by SMN1 dysfunction, and the copy number of SMN2 and NAIP can modify the phenotype of SMA. The aim of this study was to analyze the copy numbers and gene structures of SMA-related genes in Chinese SMA patients and unrelated healthy controls. METHODS: Forty-two Chinese SMA patients and two hundred and twelve unrelated healthy Chinese individuals were enrolled in our study. The copy numbers and gene structures of SMA-related genes were measured by MLPA assay. RESULTS: We identified a homozygous deletion of SMN1 in exons 7 and 8 in 37 of 42 patients (88.1%); the other 5 SMA patients (11.9%) had a single copy of SMN1 exon 8. The proportions of the 212 unrelated healthy controls with different copy numbers for the normal SMN1 gene were 1 copy in 4 individuals (1.9%), 2 copies in 203 (95.7%) and 3 copies in 5 (2.4%). Three hybrid SMN genes and five genes that lack partial sequences were found in SMA patients and healthy controls. Distributions of copy numbers for normal SMN2 and NAIP were significantly different (P < 0.001) in people with and without SMA. CONCLUSION: The copy numbers and gene structures of SMA-related genes were different in Chinese SMA patients and healthy controls.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Variações do Número de Cópias de DNA , Atrofia Muscular Espinal/genética , Proteína Inibidora de Apoptose Neuronal/genética , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Adulto , Estudos de Casos e Controles , Éxons , Feminino , Humanos , Masculino , Técnicas de Amplificação de Ácido Nucleico , Proteína 2 de Sobrevivência do Neurônio Motor/genética
9.
Blood Cells Mol Dis ; 53(4): 241-5, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24958328

RESUMO

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked incompletely dominant enzyme deficiency that results from G6PD gene mutations. Women heterozygous for G6PD mutations exhibit variation in the loss of enzyme activity but the cause of this phenotypic variation is unclear. We determined DNA methylation and X-inactivation patterns in 71 G6PD-deficient female heterozygotes and 68 G6PD non-deficient controls with the same missense mutations (G6PD Canton c.1376G>T or Kaiping c.1388G>A) to correlate determinants with variable phenotypes. Specific CpG methylations within the G6PD promoter were significantly higher in G6PD-deficient heterozygotes than in controls. Preferential X-inactivation of the G6PD wild-type allele was determined in heterozygotes. The incidence of preferential X-inactivation was 86.2% in the deficient heterozygote group and 31.7% in the non-deficient heterozygote group. A significant negative correlation was observed between X-inactivation ratios of the wild-type allele and G6PD/6-phosphogluconate dehydrogenase (6PGD) ratios in heterozygous G6PD Canton (r=-0.657, p<0.001) or Kaiping (r=-0.668, p<0.001). Multivariate logistic regression indicated that heterozygotes with hypermethylation of specific CpG sites in the G6PD promoter and preferential X-inactivation of the wild-type allele were at risk of enzyme deficiency.


Assuntos
Metilação de DNA , Variação Genética , Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/genética , Mutação de Sentido Incorreto , Inativação do Cromossomo X , Adulto , Sequência de Bases , Ilhas de CpG , Feminino , Genótipo , Deficiência de Glucosefosfato Desidrogenase/patologia , Heterozigoto , Humanos , Modelos Logísticos , Anotação de Sequência Molecular , Fenótipo , Fosfogluconato Desidrogenase/genética , Regiões Promotoras Genéticas , Fatores de Risco
10.
Gene ; 524(2): 377-80, 2013 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-23624125

RESUMO

Pretibial epidermolysis bullosa (PEB) is an extremely rare subtype of dominant dystrophic epidermolysis bullosa (DDEB) caused by mutation of the COL7A1 gene. More than 730 mutations have been identified in patients with DDEB, but only five mutations have been found to be related to PEB. In this study, a novel heterozygous nucleotide G>T transition at position 6101 in exon 73 of COL7A1 was detected, which resulted in a glycine to valine substitution (G2034V) in the triple-helical domain of type-VII collagen. This is the first report to show that one mutation caused a broad range of severity of disease in one family with PEB. These data suggest that c.6101G>T may influence the phenotype of PEB. They also contribute to the expanding database on COL7A1 mutations.


Assuntos
Colágeno Tipo VII/genética , Epidermólise Bolhosa Distrófica/genética , Mutação , Fenótipo , Adolescente , Adulto , Substituição de Aminoácidos , Grupo com Ancestrais do Continente Asiático/genética , Criança , Éxons , Feminino , Humanos , Padrões de Herança , Masculino , Pessoa de Meia-Idade , Linhagem , Índice de Gravidade de Doença , Adulto Jovem
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 30(2): 148-51, 2013 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-23568723

RESUMO

OBJECTIVE: To analyze hematological characteristics of compound heterozygotes of Hb J-Bangkok and ß-thalassemia, and to explore the influence of Hb J-Bangkok on the phenotype of ß-thalassemia. METHODS: Peripheral blood samples from a patient carrying Hb J-Bangkok and a ß-thalassemia mutation, her family members and three sporadic Hb J-Bangkok carriers were collected. RBC analysis and hemoglobin electrophoresis were performed. Genotypes of α- and ß-globin genes were analyzed. RESULTS: The father of the proband and the three sporadic cases were single carriers of Hb J-Bangkok. All of them were asymptomatic and have normal hematological parameters except for an abnormal hemoglobin band detected on hemoglobin electrophoresis. The proband was a compound heterozygote for Hb J-Bangkok and ß-thalassemia mutation IVS-Ⅱ-654. She presented typical ß-thalassemia trait, featuring hypochromic microcytic anemia and increased Hb A2 level. An abnormal hemoglobin band was also detected. CONCLUSION: Carriers of Hb J-Bangkok alone are asymptomatic. Co-existence of Hb J-Bangkok and ß-thalassemia may not aggravate the phenotype. Therefore, couples with one carrying Hb J-Bangkok and another carrying a ß-thalassemia mutation do not require prenatal diagnosis.


Assuntos
Hemoglobina J/genética , Talassemia beta/genética , Adulto , Criança , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
12.
Blood Cells Mol Dis ; 51(1): 31-4, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23481460

RESUMO

Genetic recombination has been implicated as a mechanism that drives mutagenesis in the human globin gene clusters, either as a result of unequal crossover or gene conversion. In this paper, a novel fusion gene was identified in a Chinese girl with hemoglobin H disease. The proband's father was a compound heterozygote for the common -α(4.2) deletion and this fusion gene, and her mother was heterozygous for the common --(SEA) deletion (--(SEA)/αα). Both her parents had a hypochromic and microcytic red cell phenotype and a normal hemoglobin level. Molecular studies revealed a compound heterozygote for the --(SEA) deletion and this novel fusion gene and the patient had the clinical features of classic hemoglobin H disease. Sequence analysis revealed that the mutant gene was the result of a fusion between the α2 and ψα1 genes. The recombination began at exon 3 of α2 gene, crossing with exon 3 of the ψα1 gene. With this recombination, the conservative 3'UTR of the α2 gene was changed, and an extensive transcript with a new signal 1048bp 3' to the terminating codon was found. The abnormal transcripts of the fusion gene read through the intergenic sequence.


Assuntos
Deleção de Genes , Fusão Gênica , Hemoglobina H/genética , alfa-Globinas/genética , Talassemia alfa/genética , Sequência de Bases , Pré-Escolar , Feminino , Heterozigoto , Humanos , Linhagem , Transcrição Genética , Talassemia alfa/diagnóstico
13.
BMC Evol Biol ; 13: 63, 2013 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-23497175

RESUMO

BACKGROUND: The Southeast Asian deletion (--(SEA)) is the most commonly observed mutation among diverse α-thalassemia alleles in Southeast Asia and South China. It is generally argued that mutation --(SEA), like other variants causing hemoglobin disorders, is associated with protection against malaria that is endemic in these regions. However, little evidence has been provided to support this claim. RESULTS: We first examined the genetic imprint of recent positive selection on the --(SEA) allele and flanking sequences in the human α-globin cluster, covering a genomic region spanning ~410 kb, by genotyping 28 SNPs in a Chinese population consisting of 76 --(SEA) heterozygotes and 138 normal individuals. The pattern of linkage disequilibrium (LD) and the long-range haplotype test revealed a signature of positive selection. The network of inferred haplotypes suggested a single origin of the --(SEA) allele. CONCLUSIONS: Thus, our data support the hypothesis that the --(SEA) allele has been subjected to recent balancing selection, triggered by malaria.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Cromossomos Humanos Par 16 , Hemoglobinas/genética , Malária/genética , Seleção Genética , Talassemia alfa/genética , Deleção de Genes , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Polimorfismo de Nucleotídeo Único , Recombinação Genética
15.
Artigo em Inglês | MEDLINE | ID: mdl-22727753

RESUMO

Reversed-phase high-performance liquid chromatography (RP-HPLC) of human globin chains is an important tool for detecting thalassemias and hemoglobin variants. The challenges of this method that limit its clinical application are a long analytical time and complex sample preparation. The aim of this study was to establish a simple, rapid and high-resolution RP-HPLC method for the separation of globin chains in human blood. Red blood cells from newborns and adults were diluted in deionized water and injected directly onto a micro-jupiter C18 reversed-phase column (250 mm × 4.6 mm) with UV detection at 280 nm. Under the conditions of varying pH or the HPLC gradient, the globin chains (pre-ß, ß, δ, α, (G)γ and (A)γ) were denatured and separated from the heme groups in 12 min with a retention time coefficient of variation (CV) ranging from 0.11 to 1.29% and a peak area CV between 0.32% and 4.86%. Significant differences (P<0.05) among three groups (normal, Hb H and ß thalassemia) were found in the area ratio of α/pre-ß+ß applying the rapid elution procedure, while P≥0.05 was obtained between the normal and α thalassemia silent/trait group. Based on the ANOVA results, receiver operating characteristic (ROC) curve analysis of the δ/ß and α/pre-ß+ß area ratios showed a sensitivity of 100.0%, and a specificity of 100.0% for indicating ß thalassemia carriers, and a sensitivity of 96.6% and a specificity of 89.6% for the prediction of hemoglobin H (Hb H) disease. The proposed cut-off was 0.026 of δ/ß for ß thalassemia carriers and 0.626 of α/pre-ß+ß for Hb H disease. In addition, abnormal hemoglobin hemoglobin E (Hb E) and Hb Westmead (Hb WS) were successfully identified using this RP-HPLC method. Our experience in developing this RP-HPLC method for the rapid separation of human globin chains could be of use for similar work.


Assuntos
Cromatografia de Fase Reversa/métodos , Subunidades de Hemoglobina/análise , Hemoglobinas Anormais/análise , Adulto , Análise de Variância , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão/métodos , Heme/química , Subunidades de Hemoglobina/química , Subunidades de Hemoglobina/classificação , Hemoglobinas Anormais/química , Hemoglobinas Anormais/classificação , Humanos , Concentração de Íons de Hidrogênio , Recém-Nascido , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Talassemia/sangue , Talassemia alfa/sangue
16.
Anal Biochem ; 427(2): 144-50, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-22617799

RESUMO

Increasing evidence indicates that copy number variants (CNVs) have great relevance to common human diseases. In α-thalassemia, clinical phenotypes are related to genotypes, specifically copy number changes in the human α-globin gene cluster. Assays are available for high-throughput screening of unknown CNVs genome-wide and also for targeted CNV genotyping at loci associated with genetic disorders. Here we describe a universal quantitative approach based on nested real-time quantitative polymerase chain reaction for accurate determination of copy numbers at multiple particular gene loci. We used the α-globin gene as a model system, obtaining the reproducibility and sensitivity to analyze different gene copies and testing 95 DNA samples with 16 different known genotypes. Our results showed that this approach has high sensitivity and low standard deviations for correctly genotyping DNA samples containing different copy numbers of the α1 and α2 globin genes. Our method is rapid, simple, and reliable, and it could be used to simultaneously screen for α-thalassemia deletions or triplications. Moreover, it has potential as a versatile technology for the rapid genotyping of known CNVs in a targeted region.


Assuntos
Variações do Número de Cópias de DNA , Impressões Digitais de DNA/métodos , Deleção de Sequência , alfa-Globinas/genética , Talassemia alfa/genética , Sequência de Bases , Amplificação de Genes , Dosagem de Genes , Loci Gênicos , Genótipo , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Multiplex , Mutação , Isoformas de Proteínas/genética , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Zhonghua Fu Chan Ke Za Zhi ; 47(2): 90-5, 2012 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-22455738

RESUMO

OBJECTIVE: To report the results of preventive control program of severe thalassemias in Zhuhai City of Guangdong Province from 1998 to 2010. METHODS: As the guide centre of marriage and childbearing and the greatest maternity hospital in Zhuhai City of Guangdong Province, Zhuhai Municipal Maternity and Child Healthcare Hospital constructed the genetic screening network for thalassemias testing and referred for follow-up and for genetic counseling. The couples for premarital medical examination or regular healthcare examination in pregnancy were enrolled to this preventive control program. A conventional strategy of screening for heterozygote was used to identify the α- and ß-thalassemia traits in women and their spouses according to the standard procedures of hematological phenotype analysis which was recommended by Thalassemia International Federation (TIF). Then those suspected couples at risk were diagnosed for α- and ß-thalassemia by PCR-based DNA assays. The couples at risk for severe thalassemias were counseled and offered prenatal diagnosis and termination of pregnancy in case of an affected fetus in the rights of consent and of option voluntarily. RESULTS: From January 1998 to December 2010, 85 522 brides and grooms-to-be for premarital screening and 41 503 pregnant women in addition to 14 141 partners for prenatal screening were recorded, the covering rates of premarital screening and prenatal screening in the city were 92.698% (from 1998 to 2003) and 27.667% (from 2004 to 2010), respectively. Totally 10 726 cases were found to be the carriers of thalassemias, with 7393 for α-thalassemia (5.237%, 7 393/141 166) and 3333 for ß-thalassemia (2.361%, 3 333/141 166). A total of 257 couples at-risk for severe thalassemias were detected including 190 for α-thalassemia and 67 for ß-thalassemia. Among them, 251 (97.7%, 251/257) couples were performed prenatal diagnosis. During the preventive control program, a total of 72 fetuses with severe thalassemias including hemoglobin H disease were voluntarily terminated. In Zhuhai City, the average annual birth rate of fetuses with severe thalassemia was declined by 32.9% (49/149). CONCLUSIONS: This study has reduced effectively birth rate of perinatal infants with severe thalassemias in Zhuhai City by genetic screening and prenatal diagnosis of thalassemia in the large population of 13 years. Our summary comes out of technical proposals for prenatal screening and diagnosis, which could be take example by preventative control of thalassemia in other regions of China where are prevalent.


Assuntos
Testes Genéticos/métodos , Diagnóstico Pré-Natal/métodos , Talassemia alfa/diagnóstico , Talassemia alfa/epidemiologia , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia , Adulto , China/epidemiologia , Feminino , Aconselhamento Genético , Heterozigoto , Humanos , Lactente , Masculino , Reação em Cadeia da Polimerase/métodos , Gravidez , Exames Pré-Nupciais , Prevalência , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Talassemia alfa/genética , Talassemia alfa/prevenção & controle , Talassemia beta/genética , Talassemia beta/prevenção & controle
19.
Zhonghua Xue Ye Xue Za Zhi ; 33(10): 856-60, 2012 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-23384911

RESUMO

OBJECTIVE: To investigate the hematological characteristics of co-inheritance of α-thalassemia (α-thal) and ß-thalassemia (ß-thal) and to survey the incidence of co-inheritance of α-thal and ß-thal in Guangxi. METHODS: DNA samples from 370 primary and middle school students who were ß-thal carriers in Guangxi were further processed for the α-goblin gene mutation screening, and were grouped based on the genotype of ß- and α-goblin gene. The hematological indexes to the different groups were compared by One-way ANOVA. RESULTS: Of the total 370 ß-thal carriers, 79 were found to carry α-thal, which gave a frequency of 21.35% for ß-thal carriers and 1.36% for coincidence of these two common disorders in the local population. As expected, the 79 patients presented very variable α-globin alterations in combination with ß-globin mutations, showing 31 genotype combined with the coincidence of both Hb disorders. Except the genotypes of 3 ß-thal heterozygotes combined with ααα(anti3.7) triplication and 2 ß-thal carriers with IVS-II-654(C→T)/N combined-α(3.7)/αα presented the phenotype of thalassemia intermedia, and other 74 carriers with co-inheritance of α-thal and ß-thal all presented the phenotype of ß-thal trait. There were significant differences between ß-thal heterozygotes and the carriers with a co-inheritance of both ß+α(0) thal in MCH, MCV and Hb. In addition, there existed significant difference between the carriers with a co-inheritance of both ß+α(+) thal and a co-inheritance of both ß+α(0) thal in MCV, MCH and Hb. CONCLUSION: Compared to that of ß-thal heterozygotes, the carriers with a co-inheritance of α-thal and ß-thal had slighter phenotype with hematological characteristics. It's difficult to distinguish the double heterozygotes with the co-inheritance of α-thal and ß-thal from ß-thal heterozygotes by hematological indexes, the molecular diagnosis should be performed.


Assuntos
Talassemia alfa/genética , Talassemia beta/genética , Criança , China/epidemiologia , Feminino , Frequência do Gene , Genótipo , Humanos , Incidência , Masculino , Talassemia alfa/sangue , Talassemia alfa/epidemiologia , Talassemia beta/sangue , Talassemia beta/epidemiologia
20.
PLoS One ; 6(9): e24779, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21980356

RESUMO

Reliable detection of large deletions from cell-free fetal DNA (cffDNA) in maternal plasma is challenging, especially when both parents have the same deletion owing to a lack of specific markers for fetal genotyping. In order to evaluate the efficacy of a non-invasive prenatal diagnosis (NIPD) test to exclude α-thalassemia major that uses SNPs linked to the normal paternal α-globin allele, we established a novel protocol to reliably detect paternal SNPs within the (--(SEA)) breakpoints and performed evaluation of the diagnostic potential of the protocol in a total of 67 pregnancies, in whom plasma samples were collected prior to invasive obstetrics procedures in southern China. A group of nine SNPs identified within the deletion breakpoints were scanned to select the informative SNPs in each of the 67 couples DNA by multiplex PCR based mini-sequencing technique. The paternally inherited SNP allele from cffDNA was detected by allele specific real-time PCR. A protocol for reliable detection of paternal SNPs within the (--(SEA)) breakpoints was established and evaluation of the diagnostic potential of the protocol was performed in a total of 67 pregnancies. In 97% of the couples one or more different SNPs within the deletion breakpoint occurred between paternal and maternal alleles. Homozygosity for the (--(SEA)) deletion was accurately excluded in 33 out of 67 (49.3%, 95% CI, 25.4-78.6%) pregnancies through the implementation of the protocol. Protocol was completely concordant with the traditional reference methods, except for two cases that exhibited uncertain results due to sample hemolysis. This method could be used as a routine NIPD test to exclude gross fetal deletions in α-thalassemia major, and could further be employed to test for other diseases due to gene deletion.


Assuntos
Plasma/metabolismo , Polimorfismo de Nucleotídeo Único , Diagnóstico Pré-Natal/métodos , Talassemia alfa/genética , Adulto , Alelos , China , DNA/sangue , Feminino , Deleção de Genes , Frequência do Gene , Heterozigoto , Humanos , Masculino , Mães , Reação em Cadeia da Polimerase/métodos , Gravidez , Sensibilidade e Especificidade , Talassemia alfa/diagnóstico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA