title: Apparent gene conversions involving the SMN gene in the region of the spinal muscular atrophy locus on chromosome 5.
abstract: The survival motor neuron (SMN) gene has been described as a determining gene for spinal muscular atrophy (SMA). SMN has a closely flanking, nearly identical copy (cBCD541). Gene and copy gene can be discriminated by sequence differences in exons 7 and 8. The large majority of SMA patients show homozygous deletions of at least exons 7 and 8 of the SMN gene. A minority of patients show absence of SMN exon 7 but retention of exon 8. This is explained by results of our present analysis of 13 such patients providing evidence for apparent gene-conversion events between SMN and the centromeric copy gene. Instead of applying a separate analysis for absence or presence of SMN exons 7 and 8, we used a contiguous PCR from intron 6 to exon 8. In every case we found a chimeric gene with a fusion of exon 7 of the copy gene and exon 8 of SMN and absence of a normal SMN gene. Similar events, including the fusion counterpart, were observed in a group of controls, although in the presence of a normal SMN gene. Chimeric genes as the result of fusions of parts of SMN and cBCD541 apparently are far from rare and may partly explain the frequently observed SMN deletions in SMA patients.
authors.affiliation: Department of Medical Genetics, University of Groningen, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: van der Steege
authors.forename: P M
authors.initials: PM
authors.lastname: Grootscholten
authors.forename: J M
authors.initials: JM
authors.lastname: Cobben
authors.forename: S
authors.initials: S
authors.lastname: Zappata
authors.forename: H
authors.initials: H
authors.lastname: Scheffer
authors.forename: J T
authors.initials: JT
authors.lastname: den Dunnen
authors.forename: G J
authors.initials: GJ
authors.lastname: van Ommen
authors.forename: C
authors.initials: C
authors.lastname: Brahe
authors.forename: C H
authors.initials: CH
authors.lastname: Buys
mesh_terms: D002895:Chromosomes, Human, Pair 5; D017362:Cyclic AMP Response Element-Binding Protein; D004587:Electrophoresis, Agar Gel; D005091:Exons; D005785:Gene Conversion; D006801:Humans; D007438:Introns; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins; D015183:Restriction Mapping; D055532:SMN Complex Proteins
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins