RESUMEN
Dominant GJB2 mutations are known to cause a syndromic form of sensorineural hearing loss associated with palmo-plantar skin manifestations. We present the genotype/phenotype correlations of a new GJB2 mutation identified in three generations of an Italian family (proband, mother and grandfather) whose members are affected by sensorineural hearing impairment associated with adult-onset palmoplantar keratoderma. In all affected members we identified a new heterozygous GJB2 mutation (c.66G > T, p.Lys22Asn) whose segregation, population frequency and in silico prediction analysis have suggested a pathogenic role. The p.Lys22Asn GJB2 mutation causes a dominant form of hearing loss associated with variable expression of palmoplantar keratoderma, representing a model of full penetrance, with an age-dependent effect on the phenotype.
Asunto(s)
Conexinas/genética , Pérdida Auditiva Sensorineural/genética , Queratodermia Palmoplantar/genética , Mutación , Anciano , Niño , Conexina 26 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Adulto JovenRESUMEN
Cell-free fetal DNA in maternal plasma or serum is at present widely investigated as a source of fetal genetic material, both in studies of pregnancy-related disorders and in planning strategies for non-invasive prenatal diagnosis. Despite the number of trials already performed on the quantitation of fetal DNA, data about the amount of DNA at the beginning of pregnancy, in particular in the first trimester, remain limited. A new probe mapping on the deleted in azoospermia (DAZ) repetitive region of the Yq chromosome was designed for an early assessment of fetal DNA concentration in maternal serum. Among 57 pregnant women prospectively studied in their first trimester, fetal DNA was detected already by the 5th gestational week, with the analysis becoming reliable by the 8th week of gestation when a 100% accuracy in fetal sex determination was achieved. Moreover, in the three cases of pregnancy ending in fetal loss, the amount of fetal DNA apparently decreased before the abortion was diagnosed, whereas it consistently showed an increasing trend in normal pregnancies. Real-time PCR with the use of DAZ multilocus probe can efficiently quantitate free fetal DNA in the maternal serum at the beginning of pregnancy.