Identification of de novo Mutations of Duchénnè/Becker Muscular Dystrophies in Southern Spain

Background: Duchénnè/Becker muscular dystrophies (DMD/BMD) are X-linked diseases, which are caused by a de novo gene mutation in one-third of affected males. The study objectives were to determine the incidence of DMD/BMD in Andalusia (Spain) and to establish the percentage of affected males in whom a de novo gene mutation was responsible.Methods: Multiplex ligation-dependent probe amplification (MLPA) technology was applied to determine the incidence of DMD/BMD in 84 males with suspicion of the disease and 106 female relatives.Results: Dystrophin gene exon deletion (89.5%) or duplication (10.5%) was detected in 38 of the 84 males by MLPA technology; de novo mutations account for 4 (16.7%) of the 24 mother-son pairs studied.Conclusions: MLPA technology is adequate for the molecular diagnosis of DMD/BMD and establishes whether the mother carries the molecular alteration responsible for the disease, a highly relevant issue for genetic counseling.CGLL has a postdoctoral fellowship from the Plan Propio of the University of Granada

Desarrollo de un nuevo método para la detección de las mutaciones más frecuentes en los principales genes implicados en la trombofilia hereditaria

Tesis Univ. Granada. Departamento de Bioquímica y Biología Molecular III e Inmunología. Leída el 17 de junio de 201

Adjusting the dose of tamoxifen in patients with early breast cancer and CYP2D6 poor metabolizer phenotype

CYP2D6 is a key enzyme in tamoxifen metabolism, transforming it into its main activemetabolite, endoxifen. Poor CYP2D6 metabolizers (PM) have lower endoxifen plasma concentrations and possibly benefit less from treatment with tamoxifen. We evaluated tamoxifen dose adjustment in CYP2D6 PM patients in order to obtain plasma concentrations of endoxifen comparable to patients with extensive CYP2D6 metabolism (EM). Comprehensive CYP2D6 genotyping and plasma tamoxifen metabolite concentrations were performed among 249 breast cancer patients in adjuvant treatment with tamoxifen. Tamoxifen dose was increased in PM patients to 40 mg and to 60 mg daily for a 4-month period each, repeating tamoxifen metabolite measurements on completion of each dose increase. We compared the endoxifen levels between EM and PM patients, and among the PM patients at each dose level of tamoxifen (20, 40 and 60 mg). Eleven PM patients (4.7%) were identified. The mean baseline endoxifen concentration in EM patients (11.30 ng/ml) was higher compared to the PM patients (2.33 ng/ml; p < 0.001). In relation to the 20 mg dose, increasing the tamoxifen dose to 40 and 60 mg in PM patients significantly raised the endoxifen concentration to 8.38 ng/ml (OR 3.59; p ¼ 0.013) and to 9.30 ng/ml (OR 3.99; p ¼ 0.007), respectively. These concentrations were comparable to those observed in EM patients receiving 20 mg of tamoxifen (p ¼ 0.13 and p ¼ 0.64, respectively). In CYP2D6 PM patients, increasing the standard tamoxifen dose two-fold or three-fold raisesendoxifen concentrations to levels similar to those of patients with EM phenotype.2.381 JCR (2014) Q2, 21/79 Obstetrics & gynecology; Q3, 129/211 OncologyUE