Spinal muscular atrophy (SMA) is a common recessive disorder characterized by 
the loss of lower motor neurons in the spinal cord. The disease has been 
classified into three types based on age of onset and severity. SMA I-III all 
map to chromosome 5q13 (refs 2,3), and nearly all patients display deletions or 
gene conversions of the survival motor neuron (SMN1) gene. Some correlation has 
been established between SMN protein levels and disease course; nevertheless, 
the genetic basis for SMA phenotypic variability remains unclear, and it has 
been postulated that the loss of an additional modifying factor contributes to 
the severity of type I SMA. Using comparative genomics to screen for such a 
factor among evolutionarily conserved sequences between mouse and human, we have 
identified a novel transcript, H4F5, which lies closer to SMN1 than any 
previously identified gene in the region. A multi-copy microsatellite marker 
that is deleted in more than 90% of type I SMA chromosomes is embedded in an 
intron of this gene, indicating that H4F5 is also highly deleted in type I SMA 
chromosomes, and thus is a candidate phenotypic modifier for SMA.