RESUMO
Duchenne muscular dystrophy (DMD) is the most common lethal hereditary neuromuscular disease. As there is no effective treatment, accurate carrier detection is essential for genetic counseling and prevention. Although linkage analysis has been widely used for this purpose, being an indirect analysis it has several limitations. Using linkage analysis for carrier detection, we found serious limitations, mainly because 82.9% of all proposita were isolated cases. We used quantitative polymerase chain reaction for direct carrier detection in families with exon deletions and found a higher than expected frequency of de novo deletions (62.2%). Furthermore, only 20.7% of the mothers of isolated deletion DMD/Becker muscular dystrophy (BMD) patients were found to be carriers. This result suggests that the Mexican population has a high frequency of de novo DMD mutations.
Assuntos
Aconselhamento Genético , Distrofias Musculares/genética , Deleção de Sequência , Creatina Quinase/sangue , Feminino , Triagem de Portadores Genéticos , Ligação Genética , Humanos , Masculino , México , Distrofias Musculares/etnologia , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
We analyzed the frequency of the G542X mutation in a sample of 76 Mexican cystic fibrosis patients and the genotype-phenotype correlation. The mutation was screened using PCR-mediated site-directed mutagenesis, and was present on 7.2% of the CF chromosomes. This frequency is significantly higher than the worldwide frequency according to the Cystic Fibrosis Genetic Analysis Consortium (3.4%, p < 0.01), and similar to that reported in Spain (8%), which is in accordance with the ethnic origin of the Mexican population. All patients carrying G542X on at least one allele had mild to moderate pulmonary disease. In patients with hepatobiliary involvement, the frequency of G542X chromosomes was higher than the frequency of the mutation in all the Mexican CF chromosomes.
Assuntos
Fibrose Cística/genética , Mutação , Sequência de Bases , Pré-Escolar , Primers do DNA , Feminino , Frequência do Gene , Humanos , Lactente , Masculino , México , Dados de Sequência Molecular , LinhagemRESUMO
We describe three delta-F508/G551S compound heterozygous siblings with a mild CF phenotype, characterized by mild chronic pulmonary disease, pancreatic sufficiency and increased sweat chloride levels. PCR-mediated site-directed mutagenesis detected the delta-F508 mutation on one allele, and the G551S mutation was detected by SSCP and sequence analysis of exon 11. Two previously described sisters who were homozygous for the G551S mutation had a very mild phenotype with normal sweat chloride concentrations. In our patients the mild phenotype resulted from the combined effect of the mild G551S allele with the severe delta-F508 allele.
Assuntos
Fibrose Cística/genética , Mutação , Adulto , Sequência de Bases , Éxons/genética , Feminino , Heterozigoto , Humanos , Masculino , Dados de Sequência Molecular , Núcleo Familiar , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo GenéticoRESUMO
We describe a compound heterozygous delta-F508/delta-I507 cystic fibrosis patient. Molecular analysis by polymerase chain reaction (PCR)-mediated site-directed mutagenesis showed the 219 bp fragment observed in delta-F508 homozygotes. The father showed a delta-F508 heterozygous pattern while the mother and sister showed a normal pattern. There were four possibilities to explain these results: a) the patient was a delta-F508/delta-I507 compound heterozygote, because the delta-I507 allele fails to amplify when analyzed with delta-F508 primers due to a double mismatch between the primers and template; b) uniparental isodisomy; c) nonmaternity; and d) sample processing mix-up. We then tested for the delta-I507 mutation using specific primers with a single base mismatch, and we found that the patient was in fact a compound heterozygote who inherited the delta-F508 mutation from the father and the delta-I507 from the mother. We underscore the need to detect this rare deletion in patients showing a delta-F508 homozygous pattern when one parent, particularly the father, is a noncarrier.