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1.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776826

RESUMO

OBJECTIVE@#To explore the genetic basis for a pedigree affected with Bartter's syndrome (BS).@*METHODS@#Panel-based next-generation sequencing (NGS) was carried out to detect mutation in BS-related genes SLC12A1, KCNJ1, BSND and CLCNKB. Sanger sequencing of MAGED2 gene and chromosomal microarray analysis (CMA) were also performed on the patient. Suspected mutation was validated in her family members.@*RESULTS@#No pathogenic mutation was detected by NGS, while a 0.152 Mb microdeletion at Xp11.21 (54 834 585-54 986 301) was found in the male fetus, which removed the entire coding region of the MAGED2 gene. His mother was a heterozygous carrier of the deletion. His father and sister did not carry the same deletion.@*CONCLUSION@#The loss of the MAGED2 gene may underlie the BS in this pedigree.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Genética , Antígenos de Neoplasias , Genética , Síndrome de Bartter , Genética , Feminino , Testes Genéticos , Heterozigoto , Humanos , Masculino , Mutação , Linhagem , Deleção de Sequência
2.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776825

RESUMO

OBJECTIVE@#To explore the genetic basis of a child featuring intellectual disability, developmental delay and epilepsy.@*METHODS@#Cytogenetic and molecular analysis including chromosomal karyotyping analysis, single nucleotide polymorphism array (SNP array) and qPCR were performed.@*RESULTS@#The karyotype of the child was determined as 46, XX; SNP array: arr [19]21q22.12q22.13(36 860 195-38 801 482)×1 dn. A heterozygous 1.9 Mb microdeletion was detected at 21q22.12q22.13. qPCR has confirmed deletion of exon 1 of the DYRK1A gene, which has occurred de novo.@*CONCLUSION@#A 21q22 deletion was diagnosed with multiple genetic methods. Genotype-phenotype correlation suggested DYRK1A to be a candidate for intellectual disability.


Assuntos
Criança , Deficiências do Desenvolvimento , Genética , Epilepsia , Genética , Estudos de Associação Genética , Humanos , Deficiência Intelectual , Genética , Cariotipagem , Proteínas Serina-Treonina Quinases , Genética , Proteínas Tirosina Quinases , Genética , Deleção de Sequência
3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776824

RESUMO

OBJECTIVE@#To correlate genotype with clinical phenotype of a child featuring multiple congenital malformations.@*METHODS@#Clinical examination of the patient was carried out. Chromosome microarray analysis (CMA) was employed to detect genomic copy number variations (CNVs), and quantitative PCR (qPCR) was used for verifying the result.@*RESULTS@#The child had congenital heart disease (ventricular septal defect, atrial septal defect, pulmonary arterial hypertension, and tricuspid regurgitation), psychomotor retardation, agenesis of corpus callosum, hypospadias and scoliosis. CMA has detected a 1.8 Mb deletion at 7p22.3, a 1.8 Mb duplication at 7p22.3p22.2 and a 23.5 Mb duplication at 7q33q36.3 in the fetus, all of which were de novo in origin.@*CONCLUSION@#CMA can precisely detect microdeletion/duplications and facilitate the genotype-phenotype correlation analysis.


Assuntos
Anormalidades Múltiplas , Genética , Criança , Cromossomos Humanos Par 7 , Genética , Variações do Número de Cópias de DNA , Testes Genéticos , Cardiopatias Congênitas , Genética , Humanos , Masculino , Fenótipo , Deleção de Sequência
4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776803

RESUMO

OBJECTIVE@#To identify potential mutations of the CLS gene in a Chinese pedigree affected with Coffin-Lowry syndrome.@*METHODS@#Whole exome sequencing was applied to detect potential mutation in the proband, and the result was verified by Sanger sequencing.@*RESULTS@#The proband was found to carry a c.966_967delAA (p.Arg323Thr fs*11) deletional mutation in the RPS6KA3 gene. The same mutation was also found in his mother.@*CONCLUSION@#The c.966_967delAA (p.Arg323Thr fs*11) deletional mutation of the RPS6KA3 gene probably underlies the disorder in this pedigree.


Assuntos
Grupo com Ancestrais do Continente Asiático , China , Síndrome de Coffin-Lowry , Genética , Humanos , Mutação , Linhagem , Proteínas Quinases S6 Ribossômicas 90-kDa , Genética , Deleção de Sequência
5.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wprim-787389

RESUMO

Cleidocranial dysplasia (CCD) is an autosomal-dominant disease characterized by the delayed closure of cranial sutures, defects in clavicle formation, supernumerary teeth, and delayed tooth eruption. Defects in the Runt-related transcription factor 2 (RUNX2), a master regulator of bone formation, have been identified in CCD patients. The aim of this study was to identify the molecular genetic causes in a CCD family with delayed tooth eruption.The 23-year-old female proband and her mother underwent clinical and radiographic examinations, and all coding exons of the RUNX2 were sequenced. Mutational analysis revealed a single nucleotide deletion mutation (NM_001024630.4 : c.357delC) in exon 3 in the proband and her mother. The single C deletion would result in a frameshift in translation and introduce a premature stop codon [p.(Asn120Thrfs*24)]. This would result in the impaired function of RUNX2 protein, which may be the cause of delayed eruption of permanent teeth in the family.


Assuntos
Clavícula , Displasia Cleidocraniana , Codificação Clínica , Códon sem Sentido , Subunidade alfa 1 de Fator de Ligação ao Core , Suturas Cranianas , Éxons , Feminino , Humanos , Biologia Molecular , Mães , Osteogênese , Deleção de Sequência , Dente , Erupção Dentária , Dente Supranumerário , Fatores de Transcrição , Adulto Jovem
6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781323

RESUMO

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.


Assuntos
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
7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781316

RESUMO

OBJECTIVE@#To explore the genetic basis for a fetus featuring increased nuchal thickness.@*METHODS@#Routine G-banding karyotyping and single nucleotide polymrophism array were carried out to detect genomic copy number variations (CNVs) in the fetus.@*RESULTS@#The fetus was found to harbor a heterozygous 3.8 Mb deletion in the 2q22.2-q22.3 region encompassing the ZEB2 gene, which is closely associated with Mowat-Wilson syndrome (MWS).@*CONCLUSION@#Haploinsufficiency of the ZEB2 gene may predispose to MWS. Lack of knowledge regarding to the ultrasonographic features of MWS may lead to misdiagnosis of the syndrome.


Assuntos
Variações do Número de Cópias de DNA , Facies , Feminino , Feto , Doença de Hirschsprung , Diagnóstico , Genética , Humanos , Deficiência Intelectual , Diagnóstico , Genética , Microcefalia , Diagnóstico , Genética , Gravidez , Diagnóstico Pré-Natal , Deleção de Sequência , Homeobox 2 de Ligação a E-box com Dedos de Zinco , Genética
8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771929

RESUMO

OBJECTIVE@#To explore the potential pathogenetic mutations of primary hypereosinophilia(HEN)by sequencing FGFR1 FLT3, MPL and JAK2 genes, and to clarify their effect on clinical manifestation and prognosis of HEN patients.@*METHODS@#The direct DNA sequencing was employed to detect the gene mutations of FGFR1, FLT3, MPL and JAK2 in HEN patients.@*RESULTS@#One deletion mutation (2654_2753del) within tyrosine kinase domain of FLT3 gene was found in a patient suffered from severe symptoms and ended with dismal outcome, which induced a premature stop codon (G885fsX888). For FGFR1, a new variation described as 1014_1019del AACAGT for nucleotide change was found in 19 cases, resulting in T339_V340del at the protein level.@*CONCLUSION@#The deletion of 6 bases in the FGFR1 gene (1014_1019del AACAGT) is first reported as non-synonymous SNP (nsSNP) site in the patients with primary hypereosinophilia. Deletion mutations in the FLT3 gene may be related with malignant clinical features and poor prognosis.


Assuntos
Sequência de Bases , Humanos , Síndrome Hipereosinofílica , Genética , Mutação , Receptores de Trombopoetina , Deleção de Sequência , Tirosina Quinase 3 Semelhante a fms
9.
Chinese Journal of Biotechnology ; (12): 458-471, 2019.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771361

RESUMO

Few tools of gene editing have been developed in Bacillus licheniformis at present. In order to enrich the tools, an FLP/FRT gene editing system that can repeatedly use a single selectable marker was constructed in Bacillus licheniformis, and the system was verified by knocking out an alpha amylase gene (amyL), an protease gene (aprE) and knocking in an exogenous Vitreoscilla hemoglobin gene (vgb). First, knock-out plasmids pNZTT-AFKF of amyL and pNZTT-EFKF of aprE were constructed using thermosensitive plasmid pNZT1 as a carrier. The two knock-out plasmids contained respective homology arms, resistance genes and FRT sites. Then the knock-out plasmids were transformed into Bacillus licheniformis and the target genes were replaced by respective deletion cassette via twice homologous exchange. Finally, an expression plasmid containing FLP recombinase reading frane was introduced and mediated the excision of resistance marker. In order to expand the practicability of the system, knock-in plasmid pNZTK-PFTF-vgb was constructed, with which knock-in of vgb at pflB site was carried out successfully. The results showed that amyL and aprE were successfully knocked out and the marker kanamycin cassette exactly excised. The activities of amylase and protease of deletion mutants were reduced by 95.3% and 80.4% respectively. vgb was successfully knocked in at pflB site and the marker tetracycline cassette excised. The expression of integrated vgb was verified via real-time PCR. It is the first time to construct an FLP/FRT system for gene editing in Bacillus licheniformis, which could provide an effective technical means for genetic modification.


Assuntos
Bacillus licheniformis , Edição de Genes , Plasmídeos , Deleção de Sequência
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771982

RESUMO

OBJECTIVE@#To provide genetic testing for two brothers with mental retardation and epilepsy.@*METHODS@#Array comparative genomic hybridization (aCGH) was used to detect copy number variations in the two patients, their parents and maternal grandparents. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was utilized to delineate the deleted region in the pedigree.@*RESULTS@#A 138 kb deletion in 15q11.2 region was detected by aCGH in both patients, which encompassed part of the UBE3A gene. MS-MLPA has narrowed down the region to exons 8 to 14 of the UBE3A gene. The same deletion was also found in their mother and grandfather.@*CONCLUSION@#The pathogenesis of this rare form of recurrent Angelman syndrome may be attributed to the partial deletion of maternal UBE3A gene.


Assuntos
Síndrome de Angelman , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Feminino , Deleção de Genes , Humanos , Masculino , Deleção de Sequência , Ubiquitina-Proteína Ligases
11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771964

RESUMO

OBJECTIVE@#To detect pathogenic variation in a pedigree affected with hereditary spastic paraplegia type 31 and explore its molecular pathogenesis.@*METHODS@#Customized Roche NimbleGen capture probes were used to capture all exons of the target genes in relation with hereditary spastic paraplegia. The DNA samples were also assayed with fluorescent quantitative PCR as well as chromosomal microarray analysis using CytoScan HD chip.@*RESULTS@#The proband and her father and grandfather were found to carry a deletion for position 85 992 693-86 842 693 on chromosome 2, which spanned approximately 900 kb and encompassed the REEP1 gene. The latter has been specifically associated with hereditary spastic paraplegia type 31. The same deletion was not found in her mother who is phenotypically normal.@*CONCLUSION@#The deletional variation of the REEP1 gene probably underlies the disease in this pedigree.


Assuntos
Feminino , Humanos , Proteínas de Membrana Transportadoras , Paraplegia , Linhagem , Deleção de Sequência , Paraplegia Espástica Hereditária , Genética
12.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-758859

RESUMO

Porcine parvovirus 7 (PPV7) was first detected in Korean pig farms in 2017. The detection rate of PPV7 DNA was 24.0% (30/125) in aborted pig fetuses and 74.9% (262/350) in finishing pigs, suggesting that PPV7 has circulated among Korean domestic pig farms. Phylogenetic analysis based on capsid protein amino acid sequences demonstrated that the nine isolated Korean strains (PPV-KA1-3 and PPV-KF1-6) were closely related to the previously reported USA and Chinese PPV7 strains. In addition, the Korean strains exhibit genetic diversity with both insertion and deletion mutations. This study contributes to the understanding of the molecular epidemiology of PPV7 in Korea.


Assuntos
Feto Abortado , Agricultura , Sequência de Aminoácidos , Grupo com Ancestrais do Continente Asiático , Proteínas do Capsídeo , DNA , Feto , Variação Genética , Humanos , Coreia (Geográfico) , Epidemiologia Molecular , Parvovirus Suíno , Deleção de Sequência , Sus scrofa , Suínos
13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-775836

RESUMO

OBJECTIVE@#To explore the characteristics of PAH gene variants among 113 phenylketonuria patients from Henan Province.@*METHODS@#The 13 exons of the PAH gene were subjected to PCR amplification and direct sequencing. Large fragment deletion and duplication of the PAH gene were detected with a multiple ligation-dependent probe amplification (MLPA) assay.@*RESULTS@#In total 195 point variants and 3 large fragment deletions were detected among the 226 alleles, with the detection rates being 86.28% and 1.33%, respectively. Variants of p.Arg243Gln (18.14%), p.Arg111X (6.19%), p.Arg53His (5.31%), EX6-96A>G (5.31%), p.Tyr356X (4.87%) and p.Val399Val (4.42%) were relatively common. Most of the variants were located in exons 7, 11, 3 and 6. Missense variations were most common. Four novel variations were detected, which included c.1016C>A (p.Ser339Tyr), c.1000T>C (p.Cys334Arg), c.1110G>T (p.Glu370Asp), and IVS6+1G>T.@*CONCLUSION@#The PAH gene variations in Henan Province have featured extensive allelic heterogeneity and variety.


Assuntos
China , Éxons , Humanos , Mutação de Sentido Incorreto , Fenilalanina Hidroxilase , Genética , Fenilcetonúrias , Genética , Mutação Puntual , Deleção de Sequência
14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-775811

RESUMO

OBJECTIVE@#To explore the molecular basis for an individual with Ax28 phenotype of the ABO subtype.@*METHODS@#The ABO group antigens on red blood cells of the proband were identified by monoclonal antibodies. The ABO antibody in serum was detected by standard A, B, O cells. Exons 1 to 7 of the ABO gene were respectively amplified by PCR and directly sequenced. Amplicons for exons 5 to 7 were also sequenced after cloning.@*RESULTS@#Weakened A antigen was detected on red blood cells from the proband. Both anti-A and anti-B antibodies were detected in the serum. Heterozygous 261G/del was detected in exon 6, while heterozygous 467C/T and 830T/C were detected in exon 7 by direct DNA sequencing. After cloning and sequencing, two alleles (O01 and Ax28) were obtained. Compared with A102, the sequence of Ax28 contained one nucleotide changes (T to C) at position 830, which resulted in amino acid change (Val to Ala) at position 277.@*CONCLUSION@#The novel mutation c.830T>C of the galactosaminyltransferase gene may give rise to the Ax28 phenotype.


Assuntos
Sistema ABO de Grupos Sanguíneos , Genética , Alelos , Substituição de Aminoácidos , Éxons , Galactosiltransferases , Genética , Genótipo , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único , Deleção de Sequência
15.
Cancer Research and Treatment ; : 1294-1303, 2018.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-717739

RESUMO

PURPOSE: The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)–mutant lung adenocarcinoma patients with acquired resistance after firstline EGFR–tyrosine kinase inhibitor (TKI) treatment. MATERIALS AND METHODS: We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFR mutation status. RESULTS: A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression-free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032). CONCLUSION: PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746-A750 mutation are associated with the frequency of T790M mutation.


Assuntos
Adenocarcinoma , Intervalo Livre de Doença , Fator de Crescimento Epidérmico , Éxons , Humanos , Neoplasias Pulmonares , Pulmão , Taxa de Mutação , Razão de Chances , Fosfotransferases , Mutação Puntual , Prevalência , Receptores ErbB , Deleção de Sequência
16.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-728828

RESUMO

Neurofibromatosis type 1 (NF1) is a common neurocutaneous syndrome that presents with multiple café-au-lait spots, skinfold freckling, dermatofibromas, neurofibromas, and Lisch nodules. Mutations of the NF1 gene, encoding the protein neurofibromin, have been identified as the cause of this disease. NF1 can also present with precocious puberty and be associated with optic pathway tumors. Hypothalamic hamartoma as the cause of precocious puberty in patients with NF1 has been rarely described in the literature. Here, we report the findings for a patient with NF1 and precocious puberty associated with a hypothalamic hamartoma who had a newly discovered 14-bp deletion mutation in exon 5 of NF1. To our knowledge, this is the first time this combination is reported in the literature.


Assuntos
Adolescente , Criança , Éxons , Genes da Neurofibromatose 1 , Hamartoma , Histiocitoma Fibroso Benigno , Humanos , Doenças Hipotalâmicas , Síndromes Neurocutâneas , Neurofibroma , Neurofibromatoses , Neurofibromatose 1 , Neurofibromina 1 , Puberdade , Puberdade Precoce , Deleção de Sequência
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-689603

RESUMO

Three boys aged 7-13 months visited the hospital due to unusual facies (prominent forehead, hypertelorism, or long mandible), motor developmental delay, and mental retardation. As for body length and head circumference, only one patient had a head circumference of >2 SD. Two patients had an advanced bone age, one had electroencephalographic abnormalities, and 3 had enlarged ventricles on head CT. The whole-genome microarray analysis showed the deletion of a copy with a size of 1.75 Mb in the chromosomal region 5q35.2 in one patient, which contained the NSD1 gene. Quantitative real-time PCR was performed for the validation of the region with copy number variation, and the results showed that the copy number of the NSD1 gene in this patient was reduced by half. High-throughput sequencing identified two heterozygous mutations, c.1157T>G and c.1177G>T, in the NSD1 gene in two patients. c.1157T>G mutations had not been reported before, but the bioinformatics analysis showed that this mutation had pathogenicity. All three boys were diagnosed with Sotos syndrome. Sotos syndrome is a congenital overgrowth syndrome with autosomal dominant inheritance; 70%-90% of patients have NSD1 gene mutations, and about 10% of patients have depletion in the 5q35 region (containing the NSD1 gene).


Assuntos
Sequência de Aminoácidos , Sequência de Bases , Variações do Número de Cópias de DNA , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intracelular , Genética , Masculino , Proteínas Nucleares , Genética , Fenótipo , Mutação Puntual , Deleção de Sequência , Síndrome de Sotos , Genética
18.
Chinese Medical Journal ; (24): 770-775, 2018.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-687040

RESUMO

<p><b>Background</b>Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are common X-linked recessive neuromuscular disorders caused by mutations in dystrophin gene. Multiplex polymerase chain reaction (multiplex PCR) and multiplex ligation-dependent probe amplification (MLPA) are the most common methods for detecting dystrophin gene mutations. This study aimed to contrast the two methods and discern the genetic characterization of patients with DMD/BMD in Eastern China.</p><p><b>Methods</b>We collected 121 probands, 64 mothers of probands, and 15 fetuses in our study. The dystrophin gene was detected by multiplex PCR primarily in 28 probands, and MLPA was used in multiplex PCR-negative cases subsequently. The dystrophin gene of the remaining 93 probands and 62 female potential carriers was tested by MLPA directly. In fetuses, multiplex PCR and MLPA were performed on 4 fetuses and 10 fetuses, respectively. In addition, sequencing was also performed in 4 probands with negative MLPA.</p><p><b>Results</b>We found that 61.98% of the subjects had genetic mutations including deletions (50.41%) and duplications (11.57%). There were 43.75% of mothers as carriers of the mutation. In 15 fetuses, 2 out of 7 male fetuses were found to be unhealthy and 2 out of 8 female fetuses were found to be carriers. Exons 3-26 and 45-52 have the maximum frequency in mutation regions. In the frequency of exons individually, exon 47 and exon 50 were the most common in deleted regions and exons 5, 6, and 7 were found most frequently in duplicated regions.</p><p><b>Conclusions</b>MLPA has better productivity and sensitivity than multiplex PCR. Prenatal diagnosis should be applied in DMD high-risk fetuses to reduce the disease incidence. Furthermore, it is the responsibility of physicians to inform female carriers the importance of prenatal diagnosis.</p>


Assuntos
China , Distrofina , Genética , Éxons , Genética , Feminino , Deleção de Genes , Heterozigoto , Humanos , Masculino , Reação em Cadeia da Polimerase Multiplex , Distrofia Muscular de Duchenne , Genética , Mutação , Genética , Gravidez , Deleção de Sequência
19.
Oman Medical Journal. 2017; 32 (1): 66-68
em Inglês | IMEMR (Mediterrâneo Oriental) | ID: emr-185728

RESUMO

Mutations in the C19 or f12 gene are known to cause mitochondrial membrane protein associated neurodegeneration [MPAN], which is a neurodegeneration with brain iron accumulation [NBIA] type 4 disorder. To the best of our knowledge, this is the first report of a genetically confirmed case of MPAN from Oman. A novel homozygous deletion of exon 2 of the C19 or f12 gene was confirmed on the proband, a seven-year old girl, who presented with gait instability. Brain magnetic resonance imaging showed iron deposition on the basal ganglia. This report highlights the importance of genetic testing of such a clinically and genetically heterogeneous condition among a population with a high consanguinity rate. To overcome the diagnostic difficulty, implementation of a cost-effective approach to perform cascade screening of carriers at risk is needed as well as programs to address risky consanguineous marriages


Assuntos
Criança , Feminino , Humanos , Encéfalo/patologia , Proteínas Mitocondriais/genética , Consanguinidade , Deleção de Sequência
20.
Acta Physiologica Sinica ; (6): 267-275, 2017.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-348275

RESUMO

Cardiac troponin T (cTnT) serves as a structural protein of myocardial fiber, and participates in heart excitation-contraction coupling process. Here, we generated tnnt2a (cTnT-coding gene) deletion mutant zebrafish via CRISPR/Cas9 technique, and performed phenotypic analysis of the identified tnnt2a mutants. We observed that there was no significant difference between heterozygous mutant and wild type zebrafish, and the homozygous mutants displayed significant malformations in heart, including cardiac arrest, atrium and ventricle enlargement, pericardium effusion, and the individuals usually died before 7 day post fertilization (dpf). We further analyzed the expression alternations of heart sarcomere genes (tnnt2a, actc1a, tpm4a, myl7, vmhc) at transcriptional level in tnnt2a(Δ2) zebrafish by performing real time RT-PCR, and found that the RNA expression level of tnnt2a in tnnt2azebrafish decreased constantly at each time point of developmental stages, and actc1a, tpm4a, myl7 and vmhc all showed higher expressions at early developmental stages and lower expressions at late developmental stages, in comparison with those of wild type zebrafish. Lastly, electron microscopy on cardiac tissues suggested that there were significant changes of the thick or thin filament structures in tnnt2a(Δ2) zebrafish, which was further confirmed by F-actin and Tpm4 immunofluorescence staining. The tnnt2azebrafish generated by CRISPR/Cas9 bears the most common symptoms of patients with dilated cardiomyopathy, and therefore can be used as a tool to study TNNT2-deficiency related cardiomyopathy.


Assuntos
Animais , Sistemas CRISPR-Cas , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Miocárdio , Patologia , Deleção de Sequência , Troponina T , Genética , Peixe-Zebra , Proteínas de Peixe-Zebra , Genética
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