Molecular analysis of the SMN and NAIP genes in Spanish spinal muscular atrophy (SMA) families and correlation between number of copies of cBCD541 and SMA phenotype [published erratum appears in Hum Mol Genet 1996 May;5(5):710]

Spinal muscular atrophy is an autosomal recessive disorder which affectsabout 1 in 10,000 individuals. The three clinical forms of SMA were mappedto the 5q13 region. Three candidate genes have been isolated and shown tobe deleted in SMA patients: the Survival Motor Neuron gene (SMN), theNeuronal Apoptosis Inhibitory Protein gene (NAIP) and the XS2G3 cDNA. Inthis report we present the molecular analysis of the SMN exons 7 and 8 andNAIP exon 5 in 65 Spanish SMA families. NAIP was mostly deleted in type Ipatients (67.9%) and SMN was deleted in 92.3% of patients with severe andmilder forms. Most patients who lacked the NAIP gene also lacked the SMNgene, but we identified one type II patient deleted for NAIP exon 5 but notfor SMN exons 7 and 8. Two other patients carried deletions of NAIP exon 5and SMN exon 7 but retained the SMN exon 8. Three polymorphic variants fromthe SMN gene, showing changes on the sequence of the centromeric (cBCD541)and telomeric copies of the SMN gene, were found. In addition, we showseveral genetic rearrangements of the telomeric SMN gene, which includeduplication of this gene in one normal chromosome, and putative geneconversion events in affected and normal chromosomes. Altogether theseresults corroborate the high genetic variability of the SMA region.Finally, we have determined the ratio between the number of centromeric andtelomeric copies of the SMN gene in parents of SMA patients, showing thatthe majority of parents of types II and III patients carried three or morecopies of the cBCD541 gene; we suggest a relationship between the number ofcopies of cBCD541 and the disease phenotype.