Prevalence of SMN1 gene duplication in different ethnic groups: implication for carrier testing

Spinal muscular atrophy (SMA) is an autosomal recessive disorder, characterized by symmetrical muscular weakness and atrophy. The incidence is variable from 1 in 6000 to 1 in 10000 live births in different geographic areas. A homozygous deletion involving exon 7 in SMN1 gene is present in more than 95% of the cases. Carrier testing in parents and relatives of SMA patients is complicated by the occurrence of SMN1 gene duplication (4-5 %). Here we report on the SMN1 genetic test results obtained in our lab in the last two years. The most frequent clinical indication is represented by positive family history for SMN1 gene deletion or SMA, partner heterozygous for the deletion and consanguinity with the partner. We calculated the frequency of different SMN1 genotypes in 326 tested subjects. We found a percentage of SMN1 gene duplications (subjects with 3 copies of SMN1) a bit higher than expected, ranging from 6 to 6.5%. The 55% of the subjects with the duplication is represented by North and West Africans that have been tested because of consanguinity with the partner, the remaining are Italians, 25% with SMA positive family history and 20% with partners heterozygous for the deletion. Our results highlight once again the importance of taking into account the occurrence of SMN1 gene duplication when performing carrier testing and suggest that the prevalence varies in different ethnic groups, therefore affecting the recurrence risk assessment