RESUMO
AIM: To present the latest findings on fragile X syndrome, the first genetic disorder identified to be caused by a new type of mutation called trinucleotide repeat expansion. DEVELOPMENT: Fragile X syndrome is the most common form of inherited mental retardation, is caused by hyperexpansion and hypermethylation of a CGG repeat tract in the FMR1 gene. In the first section we will discuss the various aspects of the gene mutation and the gene product, its phenotypic consequences in mutation carriers, diagnostic methodology, epidemiology, prevention, treatment and situation in Costa Rica. The second section deals with the recent findings in relation to the very recently described fragile X premutation tremor/ataxia syndrome, a neurodegenerative disorder affecting carriers of the mutation. CONCLUSIONS: Screening for the gene premutation in aged individuals who have tremor and balance problems is important, especially when accompanied by other signs such as parkinsonism, short term memory loss and dementia. Family genetic counselling can help those affected as well as future generations which may inherit fragile X syndrome.
Assuntos
Ataxia/complicações , Ataxia/genética , Encéfalo/fisiopatologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Síndrome do Cromossomo X Frágil/complicações , Síndrome do Cromossomo X Frágil/genética , Proteínas do Tecido Nervoso/genética , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/genética , Proteínas de Ligação a RNA/genética , Tremor/complicações , Tremor/genética , Proteína do X Frágil da Deficiência Intelectual , Frequência do Gene/genética , Humanos , Imageamento por Ressonância Magnética , Transtornos da Memória/etiologia , Memória de Curto Prazo , Fenótipo , Mutação Puntual/genética , Repetições de Trinucleotídeos/genéticaRESUMO
AIM: The aim is to review the molecular and genetic aspects of the dystrophic and no dystrophic myotonias. BACKGROUND: Myotonic diseases are hereditary conditions of the skeletal muscle, classified in two groups depending on the symptoms. In the first group are the myotonic dystrophies, with the myotonic dystrophies type 1 and 2. In the second group are the channelopathies, characterized for the affected function of the ion channels. Myotonic dystrophy type 1, a neurodegenerative, progressive and disabling disease is caused by an expansion of the CTG trinucleotide, its size shows a positive correlation with the severity and negative with age of onset. There are enough insights to think that the gain of function of the mutant ARN is the pathophysiological mechanism occurring on this disease. Myotonic dystrophy type 2, less severe than type 1, is caused by an expansion of the CCTG tetranucleotide, its pathophysiological mechanism is similar to that one proposed for the type 1. In the second group we can find the chloride channelopathies, with autosomal dominant or recessive inheritance, caused by one of the 60 different mutations on the chloride channel gene; and the sodium channelopathies, group of three clinically overlapping diseases, with dominant heredity caused by one of the 25 different mutations on the sodium channel gene. CONCLUSIONS: These diseases are highly clinically variable, and even though their genetic base is known, it is necessary too much research in order to understand their pathophisiology and the phenotype genotype relationships.
Assuntos
Transtornos Miotônicos/genética , Regiões 3' não Traduzidas/genética , Idade de Início , Canais de Cloreto/deficiência , Canais de Cloreto/genética , Cromossomos Humanos Par 19/genética , Frequência do Gene , Humanos , Canais Iônicos/deficiência , Canais Iônicos/genética , Canais Iônicos/fisiologia , Proteínas Musculares/deficiência , Proteínas Musculares/genética , Proteínas Musculares/fisiologia , Transtornos Miotônicos/classificação , Transtornos Miotônicos/epidemiologia , Distrofia Miotônica/classificação , Distrofia Miotônica/epidemiologia , Distrofia Miotônica/genética , Miotonina Proteína Quinase , Canal de Sódio Disparado por Voltagem NAV1.4 , Paralisia Periódica Hiperpotassêmica/genética , Proteínas Serina-Treonina Quinases/deficiência , Proteínas Serina-Treonina Quinases/genética , Proteínas de Ligação a RNA/genética , Canais de Sódio/deficiência , Canais de Sódio/genética , Expansão das Repetições de TrinucleotídeosRESUMO
INTRODUCTION: Myotonic dystrophy type 1 is a neuromuscular, degenerative and progressive disease, with an autosomal dominant pattern of inheritance, variable expressivity and incomplete penetrance. The genetic defect is an unstable mutation due to the expansion of the triplet CTG in the 3 unstranslated region at the DMPK gene on chromosome 19q13.3. OBJECTIVE: The main objective was to study the intergenerational behavior of the DM1 mutation in order to evaluate the importance of this disease as a neurological problem that could be manageable by genetic counseling. PATIENTS AND METHODS: The study involved 84 patients with clinical diagnosis of DM1 and their relatives, which were confirmed through molecular diagnosis using Southern blot and PCR. RESULTS: Data analysis reveals the size of the mutation presents a positive correlation with the severity of the symptoms and a negative correlation with the age of onset. Transmission of the DM1 mutation is sex and size dependent among the Costa Rican patients. There is an important increment in the size of the mutation between generations and there are no differences in mutation size respect to the transmitting sex. CONCLUSION: The worldwide intergenerational behavior of the DM1 mutation is similar in Costa Rica