RESUMO
Mediante el análisis de un caso de discordancia entre el nivel de alfa-1-antitripsina (AAT) en suero y el genotipo para los alelos deficientes más frecuentemente asociados al déficit de AAT (PI*S y PI*Z), se ha identificado por primera vez fuera de Portugal un paciente que presenta el alelo nulo PI*Q0ourém, el cual ha sido asociado a casos graves de enfisema pulmonar. La puesta a punto de un ensayo clínico para la detección de la mutación c.1130insT, basado en sondas fluorescentes de tipo HybProbe(R), ha permitido detectar otros 4 sujetos portadores del alelo PI*Q0ourém entre un conjunto de 43 pacientes que mostraban niveles séricos de AAT anormalmente bajos atendiendo a su genotipo para los alelos PI*S y PI*Z. Puesto que 4 de los 5 casos se concentran en una misma localidad de la isla de La Palma (España), es aconsejable realizar estudios genéticos familiares y quizás un cribado poblacional localizado
By analysis of a case of discrepancy between serum alpha-1-antitrypsin (AAT) level and genotype for the most common defective alleles associated with AAT deficiency (PI*S and PI*Z), a patient carrying the allele PI*Q0ourém has been identified for the first time outside of Portugal. This null allele has been implicated in cases of severe pulmonary emphysema. After developing a clinical assay for detection of c.1130insT mutation, based on fluorescent probes (HybProbe(R)), another 4 carriers of PI*Q0ourém allele were identified among 43 patients with abnormally low serum AAT levels based on their genotypes for PI*S and PI*Z alleles. Since 4 out 5 cases are from the same locality (La Palma Island, Spain), it is advisable to conduct genetic analyses of affected families and, possibly, a focused population screening
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Técnicas de Genotipagem , alfa 1-Antitripsina/genética , Deficiência de alfa 1-Antitripsina/genética , Alelos , Sequência de Bases , Degradação Associada com o Retículo Endoplasmático , Dados de Sequência Molecular , Fenótipo , Análise de Sequência de DNA , Espanha , alfa 1-Antitripsina/análiseRESUMO
By analysis of a case of discrepancy between serum alpha-1-antitrypsin (AAT) level and genotype for the most common defective alleles associated with AAT deficiency (PI*S and PI*Z), a patient carrying the allele PI*Q0ourém has been identified for the first time outside of Portugal. This null allele has been implicated in cases of severe pulmonary emphysema. After developing a clinical assay for detection of c.1130insT mutation, based on fluorescent probes (HybProbe®), another 4 carriers of PI*Q0ourém allele were identified among 43 patients with abnormally low serum AAT levels based on their genotypes for PI*S and PI*Z alleles. Since 4 out 5 cases are from the same locality (La Palma Island, Spain), it is advisable to conduct genetic analyses of affected families and, possibly, a focused population screening.
