Carrier screening for spinal muscular atrophy in Italian population

Spinal muscular atrophy (SMA) is an autosomal-recessive neuromuscular disorder characterized by motor neuron degeneration in the anterior horn of the spinal cord and brain stem, resulting in progressive muscle weakness and atrophy. The responsible survival motor neuron gene (SMN1; HGNC: 11117) is localized in 5q11.2-13.3. Screening for carriers of SMA is necessary for effective clinical/prenatal diagnosis and genetic counselling. In this study, the copy number of SMN1 gene was determined from a southern Italian population to estimate carrier frequency. This is the first report addressing the estimation of SMA carrier frequency in an Italian population. Our results show that the SMA carrier frequency in Sicily is higher than in the European populations and lower than in Mediterranean/Middle Eastern countries. The carrier testing could be a helpful tool for genetic counselling, to individuals with a positive family history. SMA is the second most common severe autosomalrecessive disorder after cystic fibrosis and the most frequent genetic cause of infant mortality, with an incidence of one per 6000–10,000 live births (Pearn 1980). Mutations in the survival motor neuron gene (SMN1; HGNC: 11117), localized in 5q11.2-13.3 within a large inverted duplicated element, cause SMA types I, II, III and IV (Lefebvre et al. 1995). Further, between 95% and 98% of individuals with recessive SMA have two deletion mutations (deletion of exons 7–8) and the remaining 2–5% have one deletion mutation (exons 7–8) and a second, different type of mutation (Ogino and Wilson 2002). People generally have between one and three copies of the SMN1 gene. Usually, people with two copies