RESUMO
The identification of mutations in Duchenne or Becker muscular dystrophy (DMD/BMD) patients is important for carrier detection in these families. We present the patterns of deletions of the dystrophin gene in Argentine population. DNA from 75 patients with DMD/BMD was analyzed by multiplex PCR and, in some cases, cDNA/Southern. Deletions were detected in 24 patients (32%) and were mainly clustered in two areas of the dystrophin gene: the 5' end (exons 3-12) and the central part (exons 44-53). 64% of the deletion endpoints lay in the middle region and 34% in the 5' end of the gene. The most frequent sites for deletion-endpoints were in the introns 47 (13.6%), 44 (11%), 2 (9%) and 12 (7%). Thus, the proportion and distribution of deletions in our DMD/BMD patients differ from those reported for other populations. Furthermore, a higher proportion of deletions was observed in familial cases (40%) than in isolated ones (30%), in contrast to previously reported data. The effect of the deletion on the reading frame agree with the phenotype in almost all the patients studied. This study will be useful in prenatal diagnosis and diagnosis of other Argentine DMD patients.
Assuntos
Deleção de Genes , Genética Populacional , Distrofias Musculares/genética , Adolescente , Adulto , Argentina , Criança , Pré-Escolar , Mapeamento Cromossômico , DNA Complementar/análise , Humanos , Masculino , Reação em Cadeia da PolimeraseRESUMO
In order to offer carrier detection, genetic counseling, and prenatal diagnosis to families with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) in our country, segregation analysis of highly polymorphic short tandem repeats (STR) (dC-dA)n: (dG-dT)n loci was utilized. The risks to females of 15 DMD BMD families (9 familial and 6 sporadic) were evaluated on STR, pedigree and serum creatine kinase (SCK) data. From the 36 females at risk of being carriers (not including 8 obligate carriers), results of STR analysis were compatible with carrier status in 7 and not compatible in 20. In 9 females, no information regarding carriership was derived from the STR analysis. Prenatal diagnosis is now possible on the carrier females. Previously identified deletions in the central part of the gene were confirmed by STR analysis in 3 families. Five new alleles were identified in Argentine individuals; allele frequencies differed from those of North American people. Results derived from this study are useful for carrier detection and genetic counseling in DMD/BMD. One case of probable mosaicism in an unaffected father was detected on a pedigree basis in a family with DMD patients.
Assuntos
Heterozigoto , Distrofias Musculares/genética , Alelos , Argentina , Creatina Quinase/genética , Feminino , Humanos , Masculino , Distrofias Musculares/enzimologia , Linhagem , Sequências de Repetição em TandemRESUMO
Duchenne muscular dystrophy and its allelic disorder Becker muscular dystrophy are among the most common hereditary human pathologies (1:3500). Two thirds of the genomic alterations responsible for these diseases involve gross gene rearrangements such as deletions, and less frequently duplications. The remaining one third includes point mutations such as deletions, insertions, and substitutions. This study describes four nonpreviously reported polymorphisms in the dystrophin gene by using the polymerase chain reaction/single-strand conformation polymorphism technique and subsequent nonisotopic silver staining.
Assuntos
Distrofina/genética , Polimorfismo Genético , Adolescente , Argentina , Sequência de Bases , Criança , Pré-Escolar , DNA/genética , Humanos , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita SimplesRESUMO
The so-called Xp21 contiguous deletion syndrome or complex glycerol kinase deficiency (GKD) usually presents with classical Duchenne muscular dystrophy (DMD) or a milder dystrophic myopathy, adrenal hypoplasia, and GKD. A number of syndromic and nonsyndromic cases of agenesis of the corpus callosum (ACC) also map to that location. To date, none of the cases of complex GKD have been associated with ACC. Here, we report on a patient with a complex phenotype as a result of the Xp21 contiguous deletion syndrome in association with ACC. Biochemical, cytogenetic, and molecular analyses were performed to detect and establish the size of the genomic deletion. It is at least 3 million base pairs in length; however, exact limits could not be determined in the present study. Nevertheless, we suggest the presence of a primary gene involved in the embryogenesis of the corpus callosum between Xp21.1 and Xp22.11.
Assuntos
Agenesia do Corpo Caloso , Deleção de Genes , Glicerol Quinase/genética , Cromossomo X , Criança , Humanos , Recém-Nascido , Masculino , SíndromeRESUMO
Sequence analysis of the TR beta gene from a patient with the syndrome of resistance to thyroid hormone revealed a novel missense mutation in exon 9, changing thymidine in position 1123 to cytosine. The corresponding amino acid alteration is a substitution of a methionine (ATG) for a threonine (ACG) at codon 313 being the patient heterozygous for the mutation. In contrast, his parents had only the wild-type sequence, suggesting a de novo mutational event.