GENE CONVERSION AT THE SMN LOCUS IN AUTOSOMAL RECESSIVE SPINAL MUSCULAR-ATROPHY DOES NOT PREDICT A MILD PHENOTYPE

Autosomal recessive proximal spinal muscular atrophy (SMA) is a diseas e of motor neuron death and a common cause of morbidity in childhood. It has been mapped to 5q13 and shown to be associated with deletions i n a gene which has been called the survival motor neuron (SMN) gene. S MN exists in two copies in 5q13 and deletions in exon 7 and 8 of the t elomeric copy (SMNtel) occur in over 90% of patients regardless of dis ease severity. In contrast, deletion of exon 7 and 8 of the centromeri c copy of SMN is present in 3-5% of the normal population. In a minori ty of patients, exon 7 but not exon 8 of SMNtel appears deleted. The p urpose of this study was to analyse this latter type of deletion in mo re detail. In all patients where there was absence of PCR amplificatio n of exon 7 but not exon 8 of SMNtel this was found to be due to repla cement with the homologous copy of SMNcen by a possible gene conversio n event. This type of mutation occurred in all grades of severity of S MA. (C) 1997 Elsevier Science B.V.