Clinical and molecular analysis of spinal muscular atrophy in Brazilian patients

Abstract

Spinal muscular atrophy (SMA), the second most common lethal autosomal recessive disorder, has an incidence of 1:10,000 newborns. SMA is divided into acute (Werdnig-Hoffmann disease, type I), intermediate (type II) and juvenile forms (KugelbergWelander disease, type III). The gene of all three forms 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 (NAIP) gene, have been identified; SMN is deleted in most SMA patients. We studied both genes in 87 Brazilian SMA patients (20 type I, 14 type II and 53 type III) from 74 unrelated families, by using PCR and single strand conformation polymorphism (SSCP). Deletions of exons 7 and/or 8 of the SMN gene were found in 69% of the families: 16/20 in type I, 9/12 in type II and 26/42 in type III. Among 51 families with deletions, 44 had both exons deleted while seven had deletions only of exon 7. Deletions of exon 5 of the NAIP gene were found in 7/20 of type I, 2/12 of type II and 1/42 of type III patients. No deletion of SMN and NAIP genes was found in 112 parents, 26 unaffected sibs and 104 normal controls. No correlation between deletions of one or both genes and phenotype severity was found.

Clinical and Genetic Study of Algerian Patients with Spinal Muscular Atrophy

“…In 5 patients, age at onset was before 18 months, which is characteristic of type II SMA , while walking capacities were compatible with SMA type III. Coexistence of various types of SMA (II and III) within a given family occurred in our series (2/57 families), as reported elsewhere [ 33 , 34 ], in favor of a continuous spectrum in childhood SMA . Additionally we found a predominance of males to females (17 female/36 males) in type III SMA , as previously reported by Rudnik-Schöneborn et al who suggested the presence of a female sparing factor [ 35 ].…”

Molecular analysis of the SMN and NAIP genes in Iranian spinal muscular atrophy patients

“…Taking the three subgroups together, the total frequency of deletions (90%) was similar to other studies reported from other populations from China, 12 Germany, 13 Japan, 14 Spain, 15 Singapore 16 and the United States. 17 A lower proportion of deletions, however, ranging from 57% to 85%, was reported in other studies in Brazil, 18 Canada, 19 Malaysia 20 and Turkey. 21 Deletions involving both exons 7 and 8 (84%) were much more frequent than deletions of only exon 7 (5.3%) or only exon 8 (1.3%).…”

Detection of Spinal Muscular Atrophy Carriers in a Sample of the Brazilian Population

“…Kim et al [28] characterized the genotype of Brazilian patients with SMA, but they did not evaluate the carrier frequency of the deleted SMN1 gene in nonrelated and healthy Brazilians with no family history of SMA.…”