Hybrid survival motor neuron genes in Japanese patients with spinal muscular atrophy

Spinal muscular atrophy (SMA) is a frequently occurring autosomal recessive disease, characterized by the degeneration of spinal cord anterior horn ce lls, leading to muscular atrophy. Most SMA patients early homozygous deleti ons of the telomeric survival motor neuron gene (SMN) exons 7 and 8. In the study presented here, we examined 20 Japanese SMA patients and found that 4 of these patients were lacking in telomeric SMN exon 7, but retained exon 8. In these 4 patients, who exhibited all grades of disease severity, dire ct sequencing analysis demonstrated the presence of a hybrid SMN gene in wh ich centromeric SMN exon 7 was adjacent to telomeric SMN exon 8. In an SMA family, a combination of polymerase chain reaction and enzyme-digestion ana lysis and haplotype analysis with the polymorphic multicopy marker Ag1-CA i ndicated that the patient inherited the hybrid gene from her father. In con clusion, hybrid SMN genes can be present in all grades of disease severity and inherited from generation to generation in an SMA family.