RESUMEN
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.
Asunto(s)
Adolescente , Adulto , Niño , Preescolar , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Análisis Mutacional de ADN/métodos , Exones , Femenino , Eliminación de Gen , Humanos , India/epidemiología , Lactante , Masculino , Datos de Secuencia Molecular , Atrofia Muscular Espinal/clasificación , Proteínas del Tejido Nervioso/genética , Proteína Inhibidora de la Apoptosis Neuronal/genética , Polimorfismo de Longitud del Fragmento de Restricción , Estudios Prospectivos , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Proteínas del Complejo SMN , Proteína 1 para la Supervivencia de la Neurona MotoraRESUMEN
A seven-year-old boy presented with a second episode of acute transverse myelopathy. The first episode had responded dramatically to methylprednisolone. The manifestations of the second episode did not respond to methylprednisolone or IVIG. He showed persistently raised levels of antiphospholipid antibodies in the serum. Primary conditions like collagen vascular diseases, malignancy, exposure to drugs and HIV infection, which are known to be associated with the raised titers of these antibodies were ruled out clinically and by investigations. Recurrent transverse myelopathy is a rare event in childhood and reports of its association with Antiphospholipid Antibody Syndrome (APLAS) are scanty. The etiological role for these antibodies remains to be established. However, once the diagnosis is established, it may be prudent to treat the condition with agents and procedures to bring about a decrease in their titers. Long-term therapy to prevent thromboembolic complications of APLAS may also be instituted.