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1.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781299

RESUMO

OBJECTIVE@#To determine the frequency, common chromosomal karyotypes and breakpoints, and involved regions among carriers of reciprocal translocations from Henan Province, and to explore the influence of common breakpoint regions on pregnancy and fetal development.@*METHODS@#For 586 carriers of reciprocal translocations, the above features were retrospectively analyzed.@*RESULTS@#The 586 reciprocal translocations were identified among 62 477 subjects, which yielded a frequency of 0.94%. Among these, 572 (0.92%) had abnormal fertility, and 14 (0.02%) had a history of abnormal fetal development. Statistical analysis showed that chromosomes 1, 4, 7 and 11 were most frequently involved, with t(11;22)(q25;q13) being the most common type of translocation. In total 437 breakpoint regions were identified, with 11q23, 22q13 and 1p36 being most frequently involved, which resulted in infertility, abortion, embryo death, congenital malformation, development delay, mental retardation or a normal phenotype.@*CONCLUSION@#Above results indicated a 0.92% carrier rate for reciprocal chromosomal translocations in Henan. The location of breakpoint regions may affect the pregnancy and/or fetal development. Discovery of such regions may enable more accurate genetic, reproductive and developmental counseling for carriers, and provide reference for delineation of function and pathogenetic mechanism of the relevant genes.


Assuntos
Pontos de Quebra do Cromossomo , Feminino , Heterozigoto , Humanos , Cariótipo , Cariotipagem , Gravidez , Estudos Retrospectivos , Translocação Genética , Genética
2.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781298

RESUMO

OBJECTIVE@#To explore the genetic basis of a patient featuring global developmental delay, intellectual disability, cleft palate, seizures and hypotonia.@*METHODS@#Clinical examination and laboratory tests were carried out. Peripheral blood samples were obtained from the patient and his parents. Whole genomic DNA was extracted and subjected to next generation sequencing. Candidate variation was analyzed by using bioinformatic software and validated by Sanger sequencing.@*RESULTS@#The proband was found to carry a heterozygous c.2117T>C (p.Leu706Pro) variant of the NEDD4L gene, which was a de novo variant validated by Sanger sequencing and predicted to be likely pathogenic according to the American College of Medical Genetics Guidelines.@*CONCLUSION@#The heterozygous variant of c.2117T>C (p.Leu706Pro) of the NEDD4L gene probably underlies the disorders in the patient.


Assuntos
Testes Genéticos , Heterozigoto , Humanos , Deficiência Intelectual , Genética , Masculino , Mutação , Ubiquitina-Proteína Ligases Nedd4 , Genética , Heterotopia Nodular Periventricular , Genética
3.
An. bras. dermatol ; 94(6): 658-663, Nov.-Dec. 2019. tab, graf
Artigo em Inglês | LILACS (Américas) | ID: biblio-1054887

RESUMO

Abstract Background: Palmoplantar pustulosis is considered to be a localized pustular psoriasis confined to the palms and soles. Mutation of the IL36RN gene, encoding interleukin-36 receptor antagonist (IL-36Ra), is associated with generalized pustular psoriasis, but IL36RN mutations in Chinese palmoplantar pustulosis patients have not previously been investigated. Objective: The aim of this study was to evaluate the mutation of IL36RN in Chinese patients with palmoplantar pustulosis. Methods: Fifty-one Han Chinese patients with palmoplantar pustulosis were recruited. All exons and exon-intron boundary sequences of IL36RN were amplified in polymerase chain reactions, and Sanger sequencing of the amplicons was performed. Results: Among the 51 palmoplantar pustulosis patients, four different single-base substitutions were identified in nine patients. The mutations were c.140A>G/p.Asn47Ser in five patients, c.258G>A/p.Met86IIe in two patients, and c.115+6T>C and c.169G>A/p.Val57IIe in one patient each. All mutations were heterozygous. Comparison with the human genome database and reported literature suggested that these variants may not be pathogenic mutations causing palmoplantar pustulosis. Furthermore, there was no difference in disease severity, onset age, or disease duration between patients with these heterozygous IL36RN variants and those without (p > 0.1). Study limitation: Lack of the further evaluation of IL36Ra protein in palmoplantar pustulosis lesions. Conclusions: The four variants of IL36RN identified did not appear to be associated with the specific phenotypes of palmoplantar pustulosis.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Psoríase/genética , Interleucinas/genética , Mutação , Fenótipo , Psoríase/patologia , China , Análise de Sequência de DNA , Estatísticas não Paramétricas , Grupo com Ancestrais do Continente Asiático/genética , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Estudos de Associação Genética , Dermatoses do Pé/genética , Dermatoses do Pé/patologia , Dermatoses da Mão/genética , Dermatoses da Mão/patologia , Heterozigoto
4.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763677

RESUMO

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.


Assuntos
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
5.
Gastroenterol. latinoam ; 30(3): 141-144, 2019. tab, ilus
Artigo em Espanhol | LILACS (Américas) | ID: biblio-1104465

RESUMO

Familial Mediterranean Fever is a hereditary inflammatory disease of predominantly autosomal recessive inheritance, produced by mutations in the MEFV gene that is found on the short arm of chromosome 16, characterized by recurrent episodes of fever accompanied by peritonitis, pleuritis, arthritis or erysipelaslike erythema. An episode lasts from one to three days, and its frequency is very variable. This disease is more frequent among Mediterranean populations, Jews from North Africa (not Ashkenazi), Armenians, Turks and Arabs. However, in recent years more cases have been reported in countries not related to this area. There are no formal studies of epidemiology in Chile. We present the case of one patient of Egyptian/ Jewish ancestry, and the case of a family of German/Spanish ancestry, all Chileans with semiology and characteristic evolution of familial Mediterranean fever and heterozygous positive molecular study. The absence of diagnosis in non-Mediterranean countries may be due to the lack of awareness of this disease. In Chile there has been a rise in cases given by migrants and their offspring, so it is very important to keep in mind as possible diagnosis in case of pain and fever of unknown origin. On the other hand, the familial Mediterranean fever is mainly of autosomal recessive inheritance, but dominant variants have been described. Both cases described in this work present the variant in which the disease manifests itself in its heterozygous form, generating an autosomal dominant inheritance, which would increase the number of affected individuals in the population.


La fiebre mediterránea familiar es un trastorno auto inflamatorio hereditario de herencia predominantemente autosómica recesiva, producida por mutaciones en el gen MEFV que se encuentra en el brazo corto del cromosoma 16, y que se caracteriza por episodios recurrentes de fiebre acompañada de peritonitis, pleuritis, artritis o eritema tipo erisipela. Un episodio dura entre uno y tres días, y su frecuencia es muy variable. Esta enfermedad es más frecuente entre las poblaciones mediterráneas, judíos del norte de África (no ashkenazíes), armenios, turcos y árabes. Sin embargo, en los últimos años se han reportado más casos en países no relacionados con esta área. No hay estudios epidemiológicos formales en Chile. Presentamos el caso de una paciente de ascendencia egipcia/judía, y el caso de una familia de ascendencia alemana/española, todos chilenos con semiología y evolución característica de fiebre mediterránea familiar y estudio molecular positivo heterocigoto. La falta de diagnóstico en países no mediterráneos puede deberse a la falta de conocimiento de esta enfermedad. En Chile han aumentado los casos dado el aumento de migrantes y sus descendientes, por lo que es importante tener este diagnóstico como posibilidad en caso de dolor y fiebre de origen desconocido. Por otro lado, la fiebre mediterránea familiar es principalmente de herencia autosómica recesiva, pero se han descrito variantes dominantes. Los dos casos descritos en este trabajo presentan la variante en la que la enfermedad se manifiesta en su forma heterocigota, generando una herencia autosómica dominante, lo que aumentaría el número de individuos afectados en la población.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Pessoa de Meia-Idade , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/genética , Febre Familiar do Mediterrâneo/tratamento farmacológico , Migrantes , Colchicina/uso terapêutico , Predisposição Genética para Doença , Pirina/genética , Heterozigoto
6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-772022

RESUMO

OBJECTIVE@#To determine the frequency of Hong Kong αα (HK αα) gene in α3.7 positive samples among carriers from Fujian area.@*METHODS@#Routine genetic testing for thalassemia was carried out for 10145 patients with positive screening results. Single PCR and two-round nested PCR were utilized to detect HK αα among 507 patients with α3.7/αα and 2 patients for whom electrophoresis showed α3.7, -αSEA and normal α2 alleles. Reverse dot blot test was used for detecting non-deletional α-thalassemia and β-thalassemia variants.@*RESULTS@#Among the 507 patients with α3.7/αα, HK αα was identified in 35 cases, which included 25 HK αα/αα, 5 HK αα/α3.7, 4 HK αα/αα with heterozygous CD41/42 (HBB: c.126_129delCTTT) variant, 1 HK αα/αα with IVS-II-654 (HBB: c.316_197C>T) heterozygous variant. One patient was confirmed to have α3.7/anti4.2 genotype. The two cases with α3.7, -αSEA and normal α2 alleles were confirmed to be HK αα/--SEA. The frequency of HK αα genotype in Fujian area was therefore 7.27% among patients with α3.7 and 0.36% in the general population.@*CONCLUSION@#A certain proportion of HK αα has been detected in Fujian area, which will enable more accurate diagnosis and genetic counseling.


Assuntos
Genótipo , Heterozigoto , Hong Kong , Humanos , Talassemia alfa , Talassemia beta
7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-772006

RESUMO

OBJECTIVE@#To identify potential mutations of F11 gene in a pedigree affected with hereditary coagulation factor XI (FXI) deficiency and explore its molecular pathogenesis.@*METHODS@#Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), coagulation factor VIII activity (FVIIIC), coagulation factor IX activity (FIXC), coagulation factor XI activity (FXIC), coagulation factor XII activity (FXIIC) and lupus anticoagulation (LA) of the proband and eight family members were determined. FXI antigen (FXIAg) was determined by enzyme-linked immunosorbent assay (ELISA). For the proband, potential mutations in the exons, flanking introns and 5'-, 3'-untranslated regions of the F11 gene were screened by direct DNA sequencing. The results were confirmed by reverse sequencing. Suspected mutations were detected in other family members. ClustalX-2.1-win and four online bioinformatic tools (PolyPhen-2, PROVEAN, SIFT, and Mutation Taster) were used to study the conservation and possible impact of the mutations. The structure of the mutational sites was processed with Swiss-PdbViewer.@*RESULTS@#The propositus had prolonged APTT (69.6 s), whose FXIC and FXIAg were reduced to 6.0% and 10.7%, respectively. Her mother, elder sister, one younger sister, little brother, daughter and son showed slightly prolonged APTT and moderate FXIC and FXIAg levels. Gene sequencing revealed that the propositus carried a heterozygous nonsense mutation c.738G>A (p.Trp228stop) in exon 7 and a heterozygous mutation c.1556G>C (p.Trp501Ser) in exon 13. Her mother, elder sister and daughter were heterozygous for the p.Trp228stop mutation, while one younger sister and little brother and son were heterozygous for p.Trp501Ser. Her husband and the youngest sister were of the wild type. Phylogenetic analysis suggested that Trp501 was highly conserved among all homologous species. The p.Trp501Ser was predicted to be "probably damaging","deleterious", "affect protein function" and "disease causing" corresponding to PolyPhen-2, PROVEAN, SIFT and Mutation Taster. Model analysis demonstrated that the non-polar Trp501 has two benzene rings, forming a hydrogen bond with Gln512 in the wild type. Once substituted by Ser501, the side chain may form another hydrogen bond with the benzene of His396. This may affect the normal space conformation and stability of FXI protein.@*CONCLUSION@#The compound heterozygous mutations of the F11 gene probably accounted for the low FXI concentration in this pedigree.


Assuntos
Fator XI , Genética , Deficiência do Fator XI , Genética , Feminino , Heterozigoto , Humanos , Masculino , Mutação , Linhagem , Filogenia
8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-772005

RESUMO

OBJECTIVE@#To explore the cause of inconsistent genotypes for an α-thalassemia carrier by using two commercial genotyping kits.@*METHODS@#GAP-PCR and PCR-reverse dot blotting (PCR-RDB) were employed to determine the genotype of the carrier, while Sanger sequencing was used to verify the results.@*RESULTS@#Sequencing analysis demonstrated that the subject has carried a α1 globin gene with a 3.7 kb heterozygous deletion. In addition, two novel mutations, IVS-II-55(T>G) and IVS-II-119(G>TCGGCCC), were found in intron 2 of α2 globin gene.@*CONCLUSION@#The two mutations located in the binding regions of PCR primers have caused failure of PCR amplification and misreading of the genotype. Combination of clinical and hematological phenotypes is indispensible to infer the genotype of carriers for accurate diagnosis.


Assuntos
Genótipo , Heterozigoto , Humanos , Mutação , Talassemia alfa , Genética
9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771993

RESUMO

OBJECTIVE@#To explore the genetic etiology of two pedigrees affected with congenital arthrogryposis.@*METHODS@#Whole exome sequencing (WES) was used to screen potential variations in the proband. Suspected variations were analyzed with bioinformatics software and validated by Sanger sequencing.@*RESULTS@#A heterozygous c.1123G>A (p.Glu375Lys) variation was detected in the proband and an affected fetus from pedigree 1, while a de novo heterozygous c.118 G>A (p.Val40Met) variation was detected in an affected fetus from pedigree 2.@*CONCLUSION@#The two heterozygous variations of the MYH3 gene probably underlie the disease in the pedigrees. Above results have facilitated genetic counseling and prenatal diagnosis.


Assuntos
Artrogripose , Proteínas do Citoesqueleto , Genética , Feminino , Heterozigoto , Humanos , Mutação , Linhagem , Gravidez , Diagnóstico Pré-Natal , Sequenciamento Completo do Exoma
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771988

RESUMO

OBJECTIVE@#To explore the genetic basis of a child affected with refractory leukocytopenia and thrombocytopenia.@*METHODS@#Clinical manifestation and auxiliary examination of the child were discussed. Whole exome next generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) were used to detected potential mutations of the FANCA gene.@*RESULTS@#Repeated blood tests indicated that the child had abnormal WBC count at (2.7-3.98)×10


Assuntos
Criança , Éxons , Proteína do Grupo de Complementação A da Anemia de Fanconi , Genética , Feminino , Heterozigoto , Humanos , Leucopenia , Genética , Mutação , Trombocitopenia , Genética
11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771963

RESUMO

OBJECTIVE@#To identify pathogenic mutation in a Chinese family affected with hereditary spastic paraplegia (HSP) through genetic testing and a follow-up survey.@*METHODS@#Whole exome sequencing was performed on DNA samples of two patients and one unaffected member to screen candidate mutations. Sanger sequencing was used to validate the suspected mutations in all ten family members.@*RESULTS@#Four patients and three asymptomatic members (under 25 years old) carried a c.1771T>C mutation of the KIAA0196, while the other three asymptomatic members (over 40 years old) did not carry the mutation. The mutation was predicted to be "affect protein function", "probably damaging" and "disease causing" by SIFT, PolyPhen-2 and Mutation Taster, respectively. Three asymptomatic carriers were followed up and one of them developed HSP one year later, while the other two had no signs of the disease yet.@*CONCLUSION@#The clinical phenotype of the c.1771T>C mutation of KIAA0196 has a considerable heterogeneity and this mutation may be a common pathogenic site of KIAA0196 mutations among Chinese patients with hereditary spastic paraplegia.


Assuntos
Adulto , Grupo com Ancestrais do Continente Asiático , Heterozigoto , Humanos , Mutação , Linhagem , Fenótipo , Proteínas , Genética , Paraplegia Espástica Hereditária , Genética
12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771936

RESUMO

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with congenital cataracts.@*METHODS@#Clinical data and peripheral blood samples were collected for the pedigree. Following extraction of genomic DNA, whole exome sequencing was carried out to detect genetic variants. Candidate variants were verified by familial co-segregation analysis and Sanger sequencing. Bioinformatics analysis was carried out to predict the function of mutant genes.@*RESULTS@#By comparing variants identified among affected and unaffected individuals, a heterozygous variant, c.110 G>C (p.R37P), was identified in exon 2 of the CRYGC gene among all patients, which also matched the criteria for potential disease-causing mutations. The result was confirmed by Sanger sequencing.@*CONCLUSION@#The c.110G>C variant of the CRYGC gene probably underlay the congenital cataracts in this pedigree.


Assuntos
Grupo com Ancestrais do Continente Asiático , Catarata , Genética , China , Heterozigoto , Humanos , Mutação , Linhagem , gama-Cristalinas , Genética
13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771864

RESUMO

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.


Assuntos
Fator VII , Deficiência do Fator VII , Feminino , Heterozigoto , Homozigoto , Humanos , Masculino , Mutação , Linhagem , Fenótipo
14.
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
15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776822

RESUMO

OBJECTIVE@#To report on a child with mental retardation caused by SYNGAP1 gene mutation.@*METHODS@#Peripheral blood samples were collected from the proband and her parents. High throughput sequencing (HTS) was employed for screening for potential mutation in the patient. Suspected mutation was validated by Sanger sequencing of the child and her parents.@*RESULTS@#By HTS, a previously unknown mutation [c.1656C>A (p.C552*)] was found in exon 10 of the SYNGAP1 gene in the proband. Sanger sequencing confirmed the heterozygous nature of the mutation and that neither of her parents carried the same mutation.@*CONCLUSION@#The dysmorphism and developmental delay of the child were probably due to the pathogenic mutation of the SYNGAP1 gene. HTS can facilitate elucidation of the genetic etiology with efficiency, which has great significance in the diagnosis, treatment and prognosis of the child.


Assuntos
Criança , Éxons , Feminino , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Deficiência Intelectual , Genética , Mutação , Proteínas Ativadoras de ras GTPase , Genética
16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776812

RESUMO

OBJECTIVE@#To explore the hematological phenotype and genotype of hemoglobin Q-Thailand in Fujian area.@*METHODS@#Genomic DNA was extracted from peripheral venous blood samples of patients. Suspected samples were screened by hematological parameters analysis and verified with DNA sequencing.@*RESULTS@#In 35 patients suspected with Hb Q-Thailand, 20 were confirmed, which included one case compounded with heterozygous β mutation and one compounded with Hb New York.@*CONCLUSION@#Analysis of hematological phenotype and genotype of Hb Q-Thailand can faciliate genetic counseling for patients from Fujian area.


Assuntos
China , Genótipo , Hemoglobinas Anormais , Genética , Heterozigoto , Humanos , Mutação , Fenótipo
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776806

RESUMO

OBJECTIVE@#To carry out genetic diagnosis for a pedigree affected with cutis laxa.@*METHODS@#Genomic DNA was extracted from peripheral blood samples from members of the pedigree and 50 unrelated healthy controls. Potential mutation was screened by next-generation sequencing and verified by Sanger sequencing.@*RESULTS@#A heterozygous c.1985delG mutation was identified in the ELN gene among all patients from this pedigree. The same mutation was not found among unaffected family members and 50 healthy controls.@*CONCLUSION@#The genetic etiology for the pedigree has been elucidated, which has enabled genetic counseling and guidance for reproduction.


Assuntos
Cútis Laxa , Genética , Elastina , Genética , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Linhagem
18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776804

RESUMO

OBJECTIVE@#To explore the molecular basis for a pedigree affected with Darier-White disease.@*METHODS@#Genomic DNA was isolated from 3 patients and 1 unaffected member from the pedigree, as well as 80 healthy controls. Targeted sequence capture and next-generation sequencing were used to screen mutations of skin disease-related genes. Candidate mutations were verified by Sanger sequencing, and co-segregation analysis was carried out to confirm the pathogenicity of mutation. Conservation analysis and protein structure and function were also predicted with Bioinformatic tools.@*RESULTS@#A heterozygous mutation c.2246G>T (p.G749V) was identified in exon 15 of ATP2A2 gene in all 3 patients from the pedigree, but not in the unaffected member or 80 healthy controls. The corresponding amino acid was highly conserved, and mutation of which can lead to structural and functional changes of the protein.@*CONCLUSION@#The c.2246G>T missense mutation of the ATP2A2 gene probably underlies the Darier-White disease in this pedigree by causing damages to the structure and function of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2).


Assuntos
Doença de Darier , Genética , Heterozigoto , Humanos , Mutação de Sentido Incorreto , Linhagem , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Genética
19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776802

RESUMO

OBJECTIVE@#To analyze the phenotype and genetic mutations in a pedigree affected with factor Ⅺ (FⅪ) deficiency.@*METHODS@#Activated partial thromboplastin time (APTT), FⅪ activity (FⅪ:C) and FⅪ antigen (FⅪ:Ag) were determined for the proband and his family members. All exons and exon-intron boundaries of the FⅪ gene of the proband were analyzed by direct sequencing. Suspected mutation was verified in his family members.@*RESULTS@#The proband had APTT of 82.4 s, FⅪ:C of 0.8%, and FⅪ:Ag of T (Lys327X) mutation in exon 10 and c.1325delT (Leu424CysfsX8) mutation in exon 12 of the FⅪ gene. His elder sister, son, daughter, two granddaughters and one grandson were heterozygous carriers of the c.1033A>T mutation, while his older sister and younger brother were heteozygous carriers of the c.1325delT mutation. Analysis using Mutation Taster software showed that both p.Lys327X and p.Leu424CysfsX8 may affect the function of protein and lead to the corresponding disease.@*CONCLUSION@#The novel mutations of Lys327X and Leu424CysfsX8 of the the FⅪ gene probably underlie the pathogenesis of congenital coagulation factor Ⅺ deficiency in this pedigree.


Assuntos
Éxons , Fator XI , Genética , Deficiência do Fator XI , Genética , Feminino , Heterozigoto , Humanos , Masculino , Mutação , Linhagem
20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776801

RESUMO

OBJECTIVE@#To explore the molecular pathogenesis for a pedigree affected with hypocalcemia secondary to hypomagnesemia.@*METHODS@#Sanger sequencing was used to detect potential variant of the TRPM6 gene in the patient and their parents.@*RESULTS@#The results showed that the patient has carried novel homozygous c.3311C>T (p.Pro1104Leu) variant of the TRMP6 gene, for which both of his parents were heterozygous carriers. Analysis of protein functions using software predicted high risk of pathogenicity.@*CONCLUSION@#The homozygous c.3311C>T (p.Pro1104Leu) variant of the TRPM6 gene probably underlies the disease in this patient.


Assuntos
Heterozigoto , Humanos , Hipocalcemia , Genética , Magnésio , Deficiência de Magnésio , Genética , Masculino , Linhagem , Canais de Cátion TRPM , Genética
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