Clinical and molecular analysis of spinal muscular atrophy in Brazilian patients

C.A Kim,M.R Passos-Bueno,C.H Gonzalez,M.J Marques-Dias,A Cerqueira,S.K Marie,U Conti,M Zatz

doi:10.1590/s1415-47571999000400005

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 (Kugelberg-Welander 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.

Highlights

Spinal muscular atrophies (SMA) include a group of motor neuron disorders characterized by degeneration of spinal cord anterior horn cells leading to muscular wasting and atrophy
The 12 patients who were still alive were all maintained by permanent mechanical ventilation, which was started from birth to 15 months
Clinical classification of SMA is helpful in providing medical care and prognostic relevance to families, but it is based on subjective and arbitrary parameters which may still be controversial and subject to errors

Summary

Introduction

Spinal muscular atrophies (SMA) include a group of motor neuron disorders characterized by degeneration of spinal cord anterior horn cells leading to muscular wasting and atrophy. The reported frequency of deletions in the NAIP gene, which has 16 exons spanning 60 kb of genomic DNA, varies in different populations from 67.9 to 0% (Chang et al, 1995; Rodrigues et al, 1996; Velasco et al, 1996) and is apparently higher in type I patients than types II and III (Cobben et al, 1995; Hahnen et al, 1995; Roy et al, 1995; Velasco et al, 1996).

Results

Conclusion