Spinal muscular atrophy (SMA) is a severe neuromuscular disease characterized by progressive muscle degeneration of the peripheral extremities. It is inherited in an autosomal recessive manner and is due to mutations of the SMN1 1 gene (Survival Motor Neuron) on chromosome 5q13. The most common mutation of this disorder, observed in more than 98% of affected individuals, is the homozygous absence/deletion of exon 7 or of exons 7 and 8 of the SMN1 gene. There is also a centromeric copy of this gene, called SMN2, with varying copy numbers ranging from zero to five. As a result of the close resemblance between the SMN1 and SMN2 genes and due to the fact that the common mutation is a deletion, detection of carriers is fairly complex and requires specialized techniques. The number of SMN2 gene copies may influence the severity of the disease.
Spinal muscular atrophy (SMA, Werdnig – Hoffmann)
We offer extended two tier testing for the disorder:
Tier 1: We perform a highly sensitive MLPA technique, for the detection of both heterozygous and homozygous deletions of exons 7 and 8 of the SMN1 gene, thus allowing reliable identification of carriers of the disorder. The test can also reveal the number of copies of the SMN2 gene, greatly assisting in clinical evaluation of affected individuals. Tier 1 testing will identify both mutations in approximately 96-98% of affected individuals.
Tier 2: We perform automated bi-directional fluorescent DNA sequencing of the entire coding region and intron/exon boundaries of the SMN1 gene, thus detecting affected individuals who are heterozygous for a deletion following Tier 1 (2-4% of patients).
NOTE: Our laboratory participates with great success in the external quality assessment scheme organized by the European Molecular Genetics Quality Network (EMQN), which is periodically applied for Spinal Muscular Atrophy (SMA).
For all prenatal molecular genetic testing, we perform analysis of polymorphic STR markers from a maternal blood sample and the fetal sample, in order to exclude any possible maternal cell contamination. Thus, for prenatal diagnosis, 1-2ml of a maternal blood sample should always accompany the fetal sample (amniotic fluid or CVS).