RESUMEN
The most common Hb D variant, Haemoglobin D (Hb D) Los Angeles is caused by a glutamic acid to glutamine substitution at codon 121 of the beta globin gene. Although asymptomatic in the heterozygous form, inheritance together with an Hb S allele can result in a severe disease similar to sickle-cell anaemia that is referred to as Hb SD disease. Prenatal diagnosis for Hb SD disease was requested by an at-risk couple of Irish/English descent. Prenatal diagnosis was performed on DNA isolated from chorionic villi at 12 weeks' gestation using dot blot and allele-specific oligonucleotide hybridization for the HbS mutation, and two independent approaches, restriction fragment analysis and ARMS (amplification refractory mutation system) for the detection of the Hb D Los Angeles mutation. The fetus was found to be heterozygous for the HbS mutation, but did not inherit the HbD mutation. Thus, a reliable and rapid prenatal diagnosis for the Hb SD disease can be achieved by molecular diagnosis.
Asunto(s)
Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/genética , Hemoglobinas Anormales/genética , Alelos , Muestra de la Vellosidad Coriónica , ADN/análisis , Análisis Mutacional de ADN , Desoxirribonucleasa EcoRI/metabolismo , Femenino , Globinas/genética , Hemoglobina Falciforme/genética , Heterocigoto , Humanos , Cariotipificación , Hibridación de Ácido Nucleico , Reacción en Cadena de la Polimerasa , EmbarazoRESUMEN
Based on breast cancer families with multiple and/or early-onset cases, estimates of the lifetime risk of breast cancer in carriers of BRCA1 or BRCA2 mutations may be as high as 85%. The risk for individuals not selected for family history or other risk factors is uncertain. We determined the frequency of the common BRCA1 (185delAG and 5382insC) and BRCA2 (6174delT) mutations in a series of 268 anonymous Ashkenazi Jewish women with breast cancer, regardless of family history or age at onset. DNA was analyzed for the three mutations by allele-specific oligonucleotide hybridization. Eight patients (3.0%, 95% confidence interval [CI] 1.5%-5.8%) were heterozygous for the 185delAG mutation, two (0.75%, 95% CI 0.20-2.7) for the 5382insC mutation, and eight (3.0%, 95% CI 1.5-5.8) for the 6174delT mutation. The lifetime risk for breast cancer in Ashkenazi Jewish carriers of the BRCA1 185delAG or BRCA2 6174delT mutations was calculated to be 36%, approximately three times the overall risk for the general population (relative risk 2.9, 95% CI 1.5-5.8). For the 5382insC mutation, because of the low number of carriers found, further studies are necessary. The results differ markedly from previous estimates based on high-risk breast cancer families and are consistent with lower estimates derived from a recent population-based study in the Baltimore area. Thus, presymptomatic screening and counseling for these common mutations in Ashkenazi Jewish women not selected for family history of breast cancer should be reconsidered until the risk associated with these mutations is firmly established, especially since early diagnostic and preventive-treatment modalities are limited.
Asunto(s)
Neoplasias de la Mama/epidemiología , Genes BRCA1/genética , Heterocigoto , Proteínas de Neoplasias/genética , Riesgo , Factores de Transcripción/genética , Adulto , Edad de Inicio , Anciano , Alelos , Proteína BRCA2 , Neoplasias de la Mama/etnología , Femenino , Frecuencia de los Genes/genética , Humanos , Judíos , Persona de Mediana Edad , Mutación/genética , Linaje , Reacción en Cadena de la PolimerasaRESUMEN
Since recent studies demonstrated the occurrence of the mitochondrial DNA (mtDNA) mutation A3243G in patients with adult-onset diabetes, an investigation was undertaken to determine the frequency of this mutation in a pediatric population with insulin-dependent diabetes mellitus (IDDM). DNA was extracted from peripheral blood of 270 pediatric patients with IDDM. The presence of the mtDNA A3243G mutation was screened for by minisequencing and mutation-specific ApaI endonuclease restriction after polymerase chain reaction (PCR) amplification of mtDNA. The A3243G mtDNA mutation was not found in any IDDM patients examined. This mutation is uncommon in children with IDDM from various ethnic and racial groups. Therefore, the contribution of the mutation to the pathogenesis of IDDM, if any, is minimal.