RESUMEN
Mutations in the X-linked androgen receptor (AR) gene cause androgen insensitivity syndrome (AIS), resulting in an impaired embryonic sex differentiation in 46,XY genetic men. Complete androgen insensitivity (CAIS) produces a female external phenotype, whereas cases with partial androgen insensitivity (PAIS) have various ambiguities of the genitalia. Mild androgen insensitivity (MAIS) is characterized by undermasculinization and gynecomastia. Here we describe a 2-month-old 46,XY female patient, with all of the characteristics of CAIS. Defects in testosterone (T) and dihydrotestosterone (DHT) synthesis were excluded. Sequencing of the AR gene showed the presence in exon 6 of a T to C transition in the second base of codon 790, nucleotide position 2369, causing a novel missense Leu790Pro mutation in the ligand-binding domain of the AR protein. The identification of a novel AR mutation in a girl with CAIS provides significant information due to the importance of missense mutations in the ligand-binding domain of the AR, which are able to induce functional abnormalities in the androgen binding capability, stabilization of active conformation, or interaction with coactivators.
Asunto(s)
Síndrome de Resistencia Androgénica/genética , Mutación Missense/genética , Receptores Androgénicos/genética , Síndrome de Resistencia Androgénica/diagnóstico , ADN/genética , Exones/genética , Femenino , Humanos , Lactante , MasculinoRESUMEN
BCR/ABL-positive acute myeloid leukemia (AML) is a rare disease, characterized by a poor prognosis, with resistance to induction chemotherapy and frequent relapses in responsive patients. Here we report a case of BCR/ABL-positive AML-M6 who, after relapse, was treated with Imatinib Mesylate (600 mg/die) and within 4 months achieved a cytogenetic and molecular complete response. After more than 4 years of continuous Imatinib therapy, nested RT-PCR for BCR/ABL is persistently negative. The case reported shows that the response obtained with Imatinib Mesylate in BCR/ABL-positive AML may be long lasting, offering a chance of successful treatment for this poor prognosis group of patients.
Asunto(s)
Antineoplásicos/uso terapéutico , Proteínas de Fusión bcr-abl/genética , Leucemia Eritroblástica Aguda/tratamiento farmacológico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Benzamidas , Análisis Citogenético , Femenino , Humanos , Mesilato de Imatinib , Leucemia Eritroblástica Aguda/genética , Persona de Mediana Edad , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Inducción de RemisiónRESUMEN
A patient with refractory anaemia with excess of blasts (RAEB) had a complex karyotype with multiple markers. Spectral karyotyping (SKY) showed rearrangements including three different der(11), containing a very high number of MLL gene copies, shown by fluorescence in situ hybridization (FISH) analysis. Fibre-FISH experiments disclosed the presence of chromatin fibres with multiple MLL copies with a head-to-tail pattern. Apparently, no other region flanking the MLL site was present in the three der(11). MLL amplification was confirmed by the reverse transcription polymerase chain reaction (RT-PCR). The patient died 6 months after diagnosis, supporting the severe prognosis of sole MLL amplification.