DE-NOVO AND INHERITED DELETIONS OF THE 5Q13 REGION IN SPINAL MUSCULARATROPHIES

Spinal muscular atrophies (SMAs) represent the second most common fata l autosomal recessive disorder after cystic fibrosis. Childhood spinal muscular atrophies are divided into severe (type I) and mild forms (t ypes II and III). By a combination of genetic and physical mapping, a yeast artificial chromosome contig of the 5q13 region spanning the dis ease locus was constructed that showed the presence of low copy repeat s in this region. Allele segregation was analyzed at the closest genet ic loci detected by markers C212 and C272 in 201 SMA families. Inherit ed and de novo deletions were observed in nine unrelated SMA patients. Moreover, deletions were strongly suggested in at least 18 percent of SMA type I patients by the observation of marked heterozygosity defic iency for the loci studied. These results indicate that deletion event s are statistically associated with the severe form of spinal muscular atrophy.