Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degeneration of lower motor neurons. In Romania, no statistical data regarding the incidence of disease are available. Survival motor neuron (SMN - 5q12.2-13.3) is the SMA-determining gene. The severity of SMA clinical signs may be influenced by modifier genes: SMN2, NAIP (5q12.2-13.3) and TGFb (19q13.1).

Aims: 1) to implement the molecular tests for assessing mutations in the SMN and NAIP genes in Romania and 2) to estimate the frequency of two common biallelic markers in the promoter region of TGFb gene in SMA patients and in general population.

Subjects: SMA patients (n=43), their parents (n=40) and healthy persons (n=100).

Genomic analysis. All subjects were screened for the SMN genes exons 7 and 8 deletion by PCR-RFLP, for the NAIP exon 5 deletion by PCR and for TGFb -800GA and -509CT polymorphisms by SSP-PCR.

Results and discussions: the homozygous deletion of exons 7 and 8 of the SMN1 gene was observed in 71,11% SMA patients while the NAIP exon 5 deletion was identified only in 17,7% SMA patients. The frequency of TGFb genotypes for the three groups is listed in Table 1. The Hardy-Weinberg equilibrium is respected only for the -800GA polymorphism.

Conclusions: This is the first test available in Romania for the SMA molecular diagnosis. The highest frequency of mutations was identified in SMN1 gene in SMA patients. The mutations in NAIP gene and the TGFb polymorphisms could have a modifier effect on clinical evolution of disease.

Table 1.