A NOVEL CDNA DETECTS HOMOZYGOUS MICRODELETIONS IN GREATER-THAN 50-PERCENT OF TYPE-I SPINAL MUSCULAR-ATROPHY PATIENTS

Spinal muscular atrophy (SMA) is the second most common lethal, autoso mal recessive disease in Caucasians (after cystic fibrosis). Childhood SMAs are divided into three groups (type I, II and III), which are al lelic variants of the same locus in a region of similar to 850 kb in c hromosome 5q12-q13, containing multiple copies of a novel, chromosome 5-specific repeat as well as many atypical pseudogenes. This has hampe red the identification of candidate genes. We have identified several coding sequences unique to the SMA region. A genomic fragment detected by one cDNA is homozygously deleted in 17/29 (58%) of type I SMA pati ents. Of 235 unaffected individuals examined, only two showed the dele tion and both are carriers of SMA. Our results suggest that deletion o f at least part of this novel gene is directly related to the phenotyp e of SMA.