Diagnóstico prenatal y de portadores en familia con distrofia muscular de Duchenne. Introducción de nuevos marcadores / diagnosis, prenatal and of carriers, in families with Duchenne muscular dystrophy

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[Molecular studies in Cuban patients with progressive external ophthalmoplegia]. / Estudios moleculares en pacientes cubanos con oftalmoplejía externa progresiva.

INTRODUCTION: The mitochondria, subcellular organelles which possess their own DNA (mtDNA), produce most of the energy, in the form of ATP, which is necessary for life. This mtDNA may have diverse molecular defects which have been associated with a great variety of clinical syndromes. Deletions in mtDNA are one of the common mutations in patients with mitochondrial myopathies, which in the great majority present with the common symptom of progressive external ophthalmoplegia. In this study we report our findings in eight Cuban families with suspected mitochondrial disease. OBJECTIVES: To characterize these patients from the molecular point of view, which would allow a preliminary understanding of the behavior of these deletions in Cuban patients. PATIENTS AND METHODS: We studied nine patients from eight Cuban families in whom mitochondrial encephalomyopathy was suspected. We analyzed the presence of ragged red fibres, the enzymatic activity of the mitochondrial respiratory chain and detection of mtDNA mutations. We used the technique of restriction length polymorphism analysis for detection of deletions. RESULTS: Histochemical studies showed the presence of COX negative ragged red fibres in seven of the patients studied. The enzymatic activity of the mitochondrial respiratory chain was normal in all the patients. We detected four patients with single deletions of mtDNA, and one with multiple deletions and of the patients had the A3243G mutation. CONCLUSIONS: With the methods used we were able to determine the presence of a mitochondrial disorder in seven of the eight families studied and deletions of mtDNA were detected as the cause of the illness in five. The disorder was always associated with progressive external ophthalmoplegia and COX negative ragged red fibres.

Estudios moleculares en pacientes cubanos con oftalmoplejía externa progresiva / Molecular studies in cuban patients with progressive external ophthalmoplegia

Introducción. Las mitocondrias, organelas subcelulares que poseen su propio ADN (ADNmt), producen la mayor parte de la energía, en forma de ATP, necesaria para la vida. Ese ADNmt puede presentar diversos defectos moleculares que se han asociado a una gran variabilidad de síndromes clínicos. Las deleciones en el ADNmt es una de las mutaciones comunes en pacientes con miopatías mitocondriales, los cuales, en su gran mayoría, presentan como síntoma común la oftalmoplejía externa progresiva. En este trabajo estudiamos ocho familias cubanas, en las cuales se sospechó una enfermedad mitocondrial. Objetivos. Caracterizar desde el punto de vista molecular a estos pacientes, lo que permite conocer de manera preliminar el comportamiento de las deleciones en pacientes cubanos. Pacientes y métodos. Se estudiaron nueve pacientes correspondientes a ocho familias cubanas, en las cuales se sospechaba una encefalomiopatía mitocondrial. Se analizó la presencia de fibras rojas rasgadas, la actividad enzimática de la cadena respiratoria mitocondrial y la detección de mutaciones en el ADNmt. Se utilizó la técnica de polimorfismo en longitud de los fragmentos de restricción para la detección de deleciones. Resultados. Estudios histoquímicos mostraron la presencia de fibras rojo rasgadas COX negativas en siete de los pacientes analizados. La actividad enzimática de la cadena respiratoria mitocondrial fue normal en todos los pacientes. Detectamos cuatro pacientes con deleciones únicas del ADNmt y uno con deleciones múltiples. Ninguno de los pacientes presentó la mutación puntual A3243G. Conclusiones. Con los métodos utilizados se logró definir la presencia de una enfermedad mitocondrial en siete de las ocho familias estudiadas, de las cuales en cinco se detectó deleción en el ADNmt como causa de la enfermedad. La enfermedad estuvo siempre asociada a oftalmoplejía externa progresiva y fibras rojo rasgadas COX negativas (AU)

[Werdnig-Hoffmann disease. The first prenatal diagnosis in Cuba]. / Enfermedad de Werdnig-Hoffmann. Primer diagnóstico prenatal en Cuba.

INTRODUCTION: Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by the degeneration of cells of the spinal cord. The gene was localized on chromosome 5q13 and exists in two almost identical forms, which are distinguished by the change of base on exones 7 and 8. Mutations of the gene of survival motoreneuron (SMN) are the cause of illness. CLINICAL CASE: We report, for the first time in Cuba, the prenatal diagnosis of a type II SMA carrier, using molecular methods for direct detection of the mutation on exones 7 and 8 of the SMN gene, and haplo-identification with microsatellite markers of chromosome 5q as an indirect method. A sample of amniotic liquid was taken at 18 weeks of gestation and the DNA extracted. No deletions were detected on exones 7 and 8 of the foetal DNA, which was therefore normal. CONCLUSIONS: Detection of deletions on the SMN gene is a method which permits detection of the condition (healthy or unhealthy) of the foetus, quickly and reliably, without requiring investigation of the entire family to obtain a result. The method does not require radio-active PCR, the results are clear and precise and may be obtained within 24 hours. It may also take the place of invasive methods such as muscle biopsy and electro-myography and contribute to genetic assessment in families in which there is no DNA of the affected child.