Análisis genético molecular en atrofia muscular espinal / Molecular evaluation in infantile spinal muscular atrophy

Introducción: La atrofia muscular espinal de la infancia (AMEi) es una enfermedad neurodegenerativa, causada principalmente por deleciones del gen SMN 1 en su locus 5q11.1-13.3. La severidad va desde el tipo I, que compromete la vida en edades tempranas, hasta el tipo IV. Objetivos: Se describen hallazgos moleculares en pacientes con AME, nacionalmente remitidos al Instituto de Neurología y Neurocirugía así como se reporta la frecuencia por 100.000 habitantes en cada una de las provincias de la isla. Pacientes y Métodos: 105 pacientes fueron estudiados, remitidos entre 1997 y 2011. Para la detección de las deleciones se utilizó la técnica de reacción en cadena de la polimerasa (PCR) con cebadores correspondientes a los exones 7 y 8 del gen SMN 1, y digestión con enzimas DraI y DdeI respectivamente y analizados en gel de agarosa al 2 por ciento. Resultados y Discusión: Se encontró un 59 por ciento diagnosticados como AME I, 28,6 por ciento AME II, 12,4 por ciento AME III. Del total de casos 36,2 por ciento resultaron tener deleción de los exones 7 y 8, 35,2 por ciento deleción del exón 7 solamente y 28,2 por ciento no presentaron deleción de los exones correspondientes. Se discuten dichos resultados de acuerdo a la literatura internacional. Se presentan los resultados de frecuencias por 100.000 habitantes en cada provincia del país y discuten dichas frecuencias de acuerdo a la diversidad ancestral de la población cubana. Se concluye lo novedoso del estudio que constituye el primer reporte en una población caribeña.

Introduction: Infantile Spinal Muscular Atrophy (infantile SMA) is a neurodegenerative disease caused primarily by the deletion of the SMN1 gene at 5q11.1 - 13.3. Its severity ranges from type I, in early childhood, to type IV. Objectives: To describe molecular findings in patients with SMA, who were nationally referred to the Institute of Neurology and Neurosurgery and to describe the frequency per 100,000 people in each province of the island. Patients and Methods: 105 patients, referred between 1997 and 2011, were studied. The polymerase chain reaction (PCR) technique was used to detect the deletions of exons 7 and 8 of the SMN1 gene, and DraI and DdeI enzymes, in 2 percent agarose gel, were used for digestion. Results: 59 percent of the patients were diagnosed with SMA I, 28.6 percent with SMA II and 12.4 percent with SMA III. 36.2 percent of total patients presented deletions of exons 7, 8, 35.2 percent only deletion of exon 7 and 28.2 percentdid not present deletion of exons. Conclusion: These results are discussed according to the international literature. The frequency per 100,000 inhabitants in each province is presented and discussed according to ancestral diversity of the Cuban population. Also, the originality of the study is mentioned as it is the first report of this type in a Caribbean population.

Correlation between deletion patterns of SMN and NAIP genes and the clinical features of spinal muscular atrophy in Indian patients.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder involving degeneration of anterior horn cells of spinal cord resulting in progressive muscle weakness and atrophy. AIMS: The molecular analysis of two marker genes for spinal muscular atrophy (SMA) i.e, the survival motor neuron gene (SMN) and the neuronal apoptosis inhibitory protein gene (NAIP) was conducted in 39 Indian patients with clinical symptoms of SMA. Out of these, 28 showed homozygous deletions and the phenotypic features of these SMA patients were compared with the corresponding genotypes. SETTINGS: A tertiary care teaching Hospital. DESIGN: This is a prospective hospital based study. MATERIALS AND METHODS: Polymerase chain reaction (PCR) combined with restriction fragment length polymorphism (RFLP) was used to detect the deletion of exon 7 and exon 8 of SMN1 gene, as well as multiplex PCR for exon 5 and 13 of NAIP gene. RESULTS: Exons 7 and 8 of SMN and NAIP (exon 5) were homozygously deleted in 73% of SMA I and 27% of SMA II patients. SMN exon 7 and 8 deletions without NAIP deletions were seen in 27% of type I SMA and 46% of SMA type II patients. Two patients of type III SMA showed single deletion of SMN exon 7 along with 27% of SMA type II patients. CONCLUSION: With the advent of molecular biology techniques, SMN gene deletion studies have become the first line of investigation for confirmation of a clinical diagnosis of SMA. The findings of homozygous deletions of exons 7 and/or 8 of SMN1 gene confirms the diagnosis of SMA, even in patients with atypical clinical features. Deletions of NAIP gene were mainly seen in severely affected patients, hence is useful for predicting the prognosis.

Application of DNA-based tests for diagnosis of spinal muscular atrophy in Saudi Arabia

We examined the deletion of the survival motor neuron [SMN] and neuronal apoptosis inhibitory protein [NAIP] genes in patients with spinal muscular atrophy [SMA] using polymerase chain reaction followed by restriction site assay methods. The study included 16 Saudi patients [9 SMA type I and 7 SMA type II] and 6 healthy Saudi volunteers. The homozygous deletions of exons 7 and 8 of the telomeric SMN gene, and exon 5 of the NAIP gene were found in all SMA type I patients. Exons 7 and 8 of telomeric SMN were deleted in all SMA type II patients. However, exon 5 of NAIP was deleted in three of the seven cases. All control volunteers and all family members of the patients had normal SMN and NAIP. The incidence of NAIP deletion was higher in the more severe SMA cases and the dual deletion of the SMN and NAIP genes was more common in Saudi SMA type I patients compared with patients of other ethnic groups