Asunto(s)
Pueblo Asiatico/genética , Hipotricosis/genética , Mutación Missense , Factores de Transcripción/genética , Regiones no Traducidas 5' , China , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Humanos , Hipotricosis/etnología , Hipotricosis/patología , Masculino , Sistemas de Lectura Abierta , Fenotipo , Adulto JovenRESUMEN
We report the first large genome-wide association study (GWAS) in a Chinese population to identify susceptibility variants for psoriasis using a two-stage case-control design. In the first stage, we carried out a genome-wide association analysis in 1,139 cases and 1,132 controls of Chinese Han ancestry using Illumina Human 610-Quad BeadChips. In the second stage, we took top SNPs forward for replication in two independent samples of 5,182 cases and 6,516 controls of Chinese Han ancestry, and 539 cases and 824 controls of Chinese Uygur ancestry. In addition to the strong replication for two known susceptibility loci MHC (rs1265181, P = 1.93 x 10(-208), OR = 22.62) and IL12B (rs3213094, P(combined) = 2.58 x 10(-26), OR = 0.78), we identified a new susceptibility locus within the LCE gene cluster on 1q21 (rs4085613, P(combined) = 6.69 x 10(-30), OR = 0.76).
Asunto(s)
Cromosomas Humanos Par 1 , Proteínas Ricas en Prolina del Estrato Córneo/genética , Predisposición Genética a la Enfermedad , Psoriasis/genética , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Subunidad p40 de la Interleucina-12/genética , Desequilibrio de Ligamiento , Complejo Mayor de Histocompatibilidad/genética , Masculino , Persona de Mediana Edad , Familia de Multigenes , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
OBJECTIVE: To detect the MSX1 gene mutation in a Chinese family with oligodontia. METHODS: Blood samples were obtained from seven affected and seven unaffected individuals in the pedigree. All exons and flanking intronic boundaries of the MSX1 gene were amplified with polymerase chain reaction technique and then directly sequenced. The website of bioinformatics was used to predict the effect of the mutation on the function. RESULTS: A splicing mutation (IVS1-2A > G) was found at position -2 near the 3' end of the IVS1 of MSX1, which made a change of the intron 1 splice acceptor site. None of the mutation was found in normal individuals of the family and in 100 unrelated healthy matched control individuals. CONCLUSIONS: IVS1-2A > G was a novel splicing mutation identified in the MSX-1 gene and it might be responsible for nonsyndromic oligodontia in this family.
Asunto(s)
Factor de Transcripción MSX1/genética , Mutación , Anomalías Dentarias/genética , Adolescente , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Adulto JovenRESUMEN
Hailey-Hailey disease (HHD) is an autosomal dominant skin disorder characterized by recurrent eruption of vesicles and bullae at the sites of friction and in the intertriginous areas. Mutations in the ATP2C1 gene encoding the human secretory pathway calcium ATPase 1 (hSPCA1) have been identified as the causative mutations in HHD. In this study, we used direct sequencing and restriction endonuclease digestion to analyze mutations of the ATP2C1 gene in a Chinese three-generation pedigree. A heterozygous T-to-C transition at nucleotide 1004 in exon 12 of ATP2C1 gene was detected. After summarizing the reported cases with ATP2C1 mutation, we concluded that the T1004C transition resulted in a novel missense mutation of leucine condon (CTG) to proline (CCG) at amino acid residue 335(L335P) in hSPCA1. Here, a genetic diagnosis was made for the proband's daughter before the clinical presentation. The study realized the molecular diagnosis in the HHD pedigree. Our findings should be useful for genetic counseling and prenatal diagnosis for the affected family and in demonstrating the critical role of the ATP2C1 gene in the pathogenesis of HHD further.
Asunto(s)
ATPasas Transportadoras de Calcio/genética , Mutación/genética , Pénfigo Familiar Benigno/diagnóstico , Pénfigo Familiar Benigno/genética , Adulto , Pueblo Asiatico/genética , China , Exones/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , LinajeAsunto(s)
Pueblo Asiatico/genética , Esclerosis Tuberosa/genética , Proteínas Supresoras de Tumor/genética , Salud de la Familia , Femenino , Duplicación de Gen , Humanos , Persona de Mediana Edad , Mutación , Esclerosis Tuberosa/etnología , Esclerosis Tuberosa/patología , Proteína 2 del Complejo de la Esclerosis TuberosaRESUMEN
OBJECTIVE: To study a Chinese pedigree with Hailey-Hailey disease (HHD) and examine the ATP2C1 gene mutation in this family. METHOD: All exons of ATP2C1 gene were analyzed with polymerase chain reaction and DNA sequencing in all patients of this family and 100 unrelated population-match controls. RESULTS: We identified a novel heterozygous nucleotide A --> G transition at position 235 - 2 in intron 3 of ATP2C1 gene. This splice site mutation was not found in the healthy members of this pedigree and in the controls. CONCLUSION: The splicing mutation can affect the result of transcription and translation, and it is a specific novel mutation of ATP2C1 gene.
