RESUMEN
Twenty-seven unrelated Jewish Ashkenazi patients with nonsyndromic prelingual deafness (NSD) were analyzed for mutations in the coding sequence of the connexin 26 (Cx26) gene. Biallelic mutations were identified in 19 of the 27 patients (70.4%); 12 were homozygous for the mutation 167delT, 2 were homozygous for the mutation 35delG, and 5 were compound 167delT/35delG heterozygotes. In addition three patients were heterozygous with no second identified mutation in the Cx26 gene. Biallelic mutations in the Cx26 gene account for 83% of familial cases and 44% of the sporadic cases. Among 268 unselected Ashkenazi individuals, 20 were 167delT/N heterozygotes, giving an estimate of 7.5% carrier frequency. Based on the 167delT carrier frequency in three studies (including the present one), it is expected that 167delT/167delT homozygotes account for 70% of all patients with NSD (1 in 1300). The hearing capacity of 30 patients (probands and their sibs) with biallelic Cx26 mutations and at least one allele with 167delT demonstrated inter- and intrafamilial variability from profound to mild hearing impairment.
Asunto(s)
Conexinas/genética , Sordera/genética , Judíos/genética , Eliminación de Secuencia , Alelos , Niño , Conexina 26 , ADN/química , ADN/genética , Análisis Mutacional de ADN , Sordera/patología , Salud de la Familia , Frecuencia de los Genes , Variación Genética , Genotipo , Humanos , Mutación , Fenotipo , Polimorfismo Conformacional Retorcido-SimpleRESUMEN
Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent attacks of serositis. To date more then 18 mutations responsible for the disease were identified in the MEFV gene, one such a mutation is E148Q in exon 2 of the gene. While screening FMF patients for mutations in the MEFV gene, we have identified 2 individuals parents of 2 unrelated FMF patients, who were homozygous for E148Q mutation. Upon clinical examination they were absolutely disease free and therefore raised the possibility that this mutation is a benign polymorphism rather than a mutation causing disease. To further investigate the role of the E148Q in FMF we analyzed 25 parents of FMF patients and a control group of 70 individuals, Jews of Moroccan extraction to match for ethnicity of the patients. The rate of E148Q in the control group was 6.4%, being 7.8% among the patient group. Among the parents group (obligatory carriers), in addition to the 2 parents that were homozygous E148Q, in 2 families one of the parents was heterozygote for E148Q but transmitted the other allele (apparently with unknown FMF mutation) to the affected child. Two healthy sibs of one of the E148Q homozygous were also homozygous E148Q. These observations are not in accordance to the notion that E148Q is a mutation causing disease.
Asunto(s)
Sustitución de Aminoácidos/genética , Fiebre Mediterránea Familiar/genética , Variación Genética/genética , Mutación/genética , Proteínas/genética , Adolescente , Adulto , Alelos , Niño , Proteínas del Citoesqueleto , Femenino , Ácido Glutámico/genética , Glutamina/genética , Humanos , Judíos/genética , Masculino , Persona de Mediana Edad , Marruecos , Linaje , PirinaRESUMEN
The expression of B-cell surface markers SmIg and GP-70 was determined on the mononuclear cells from the peripheral blood of 25 patients with chronic lymphocytic leukemia (CLL), 10 patients with multiple myeloma (MM), 6 normal blood donors and in 3 cases of unexplained persistent lymphocytosis. GP-70 was expressed only in CLL patients whereas multiple myeloma patients, blood donors and patients with unexplained lymphocytosis were all negative to GP-70. SmIg was expressed in CLL patients and in some of the multiple myeloma patients. Subgrouping of CLL patients to "early", stable patients (10) and to more advanced CLL patients (15) revealed differential expression of GP-70 on CLL cells from patients with more advanced stage of disease rather than in the patients with the "early" stable clinical course of disease. SmIg, on the other hand, was expressed equally on both subgroups of CLL. Furthermore, in some cases (25%) where SmIg and the light chains of Ig were only weakly expressed or were absent, GP-70 was markedly expressed. These findings suggest that GP-70 can be used as a single laboratory determination to establish clonality of the B-lymphocyte proliferation in CLL. In addition, expression of GP-70 correlates with significant clinical parameters of the disease.