Clinical and molecular analysis of spinal muscular atrophy in Brazilian patients

Spinal muscular atrophy (SMA), the second most common lethal autosomal rece ssive disorder, has an incidence of 1:10,000 newborns. SMA is divided into acute (Werdnig-Hoffmann disease, type I), intermediate (type II) and juveni le forms (Kugelberg-Welander disease, type III). The gene of all three form s of SMA maps to chromosome 5q 11.2-13.3. Two candidate genes, the survival motor neuron (SMN) gene and the neuronal apoptosis inhibitory protein (NAI P) gene, have been identified; SMN is deleted in most SMA patients. We stud ied both genes in 87 Brazilian SMA patients (20 type 1, 14 type II and 53 t ype III) from 74 unrelated families, by using PCR and single strand conform ation polymorphism (SSCP). Deletions of exons 7 and/or 8 of the SMN gene we re found in 69% of the families: 16/20 in type 1, 9/12 in type Ii and 26/42 in type Iii. Among 51 families with deletions, 44 had both exons deleted w hile seven had deletions only of exon 7. Deletions of exon 5 of the NAIP ge ne were found in 7/20 of type 1, 2/12 of type II and 1/42 of type iii patie nts. No deletion of SMN and NAIP genes was found in 112 parents, 26 unaffec ted sibs and 104 normal controls. No correlation between deletions of one o r both genes and phenotype severity was found.