RESUMO
Diagnostic testing for the fragile X syndrome is designed to detect the most common mutation, a CGG expansion in the 5'-untranslated region of the fragile X mental retardation (FMRI) gene. PCR can determine the number of CGG repeats less than 100, whereas Southern analysis can detect large premutations, full mutations, and their methylation status. Bands larger than 5.8 kb observed via Southern analysis are usually considered a methylated full mutation, causing fragile X syndrome in males and varied clinical presentations in females. We observed a 10.9-kb band on a Southern blot assay from an autistic girl with language delay. Further investigation identified a novel G-to-A transition at an EcoRI cleavage site, upstream of the CGG repeat region of the FMRI gene. This base change abolished the EcoRI restriction site, resulting in a 10.9-kb pseudo-full mutation. This G-to-A base change has not been previously reported and was not identified in a subsequent analysis of 105 male and 30 female patient samples. The clear 10.9-kb band detected on a Southern blot assay for fragile X syndrome mimics a large, methylated full mutation, which could result in a misdiagnosis without the benefit of family studies and further testing.
Assuntos
Adenosina/genética , Enzimas de Restrição-Modificação do DNA/genética , Síndrome do Cromossomo X Frágil/diagnóstico , Síndrome do Cromossomo X Frágil/genética , Mutação , Sequência de Bases , Southern Blotting , Pré-Escolar , Análise Mutacional de DNA , Feminino , Proteína do X Frágil da Deficiência Intelectual/genética , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Homologia de Sequência do Ácido Nucleico , Expansão das Repetições de Trinucleotídeos/genéticaRESUMO
The impact of advances in molecular biology over the past 25 years-especially the completion of the Human Genome Project-touches every branch of medicine and will continue to have profound influence on medical practice. Advances in genetic technology are changing the traditional patient/doctor paradigm. For some medical conditions, current genetic technology and predictive testing enable us to offer medical management before a patient is diagnosed with a disorder. However, advances in genetic technology impose on all clinicians the added requirement of identifying patients who may benefit from having access to this technology. Kaiser Permanente (KP) provides a unique, integrated approach to this challenge by serving as a model for delivery of genetic services. This article outlines the history and current status of genetic services provided in the KP Southern California Region and summarizes current and future developments in medical genetics technology.
