title: A multicopy transcription-repair gene, BTF2p44, maps to the SMA region and demonstrates SMA associated deletions.
abstract: The childhood-onset spinal muscular atrophies are a clinically heterogeneous group of autosomal recessive disorders characterized by selective degeneration of the anterior horn cells with subsequent weakness and atrophy of limb muscles. The disease locus has been mapped to a region of chromosome 5q13 characterized by genetic instability and DNA duplication. Among the duplicated genes in this region, SMNT (telomeric copy; survival motor neuron) is thought to be the major disease determining gene since it is missing in the majority of SMA patients and since small, intragenic mutations in the gene have been associated with the disorder. Approximately half of the severely affected SMA I patients are also missing both homologues of a neighboring gene, the neuronal apoptosis inhibitory protein (NAIP). These data indicate that loss of NAIP may affect disease severity and further, that the molecular events underlying the childhood-onset SMAs are complex, possibly involving multiple genes. We report a third multicopy gene in the SMA region, encoding the p44 subunit of basal transcription factor II (BTF2p44). One copy of this transcription-repair gene is deleted in at least 15% of all SMA cases.
authors.affiliation: Department of Genetics and Development, Columbia University, New York, NY, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Carter
authors.forename: C G
authors.initials: CG
authors.lastname: Bönnemann
authors.forename: C H
authors.initials: CH
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Obici
authors.forename: E
authors.initials: E
authors.lastname: Parano
authors.forename: M
authors.initials: M
authors.lastname: De Fatima Bonaldo
authors.forename: B M
authors.initials: BM
authors.lastname: Ross
authors.forename: G K
authors.initials: GK
authors.lastname: Penchaszadeh
authors.forename: A
authors.initials: A
authors.lastname: Mackenzie
authors.forename: M B
authors.initials: MB
authors.lastname: Soares
authors.forename: L M
authors.initials: LM
authors.lastname: Kunkel
authors.forename: T C
authors.initials: TC
authors.lastname: Gilliam
mesh_terms: D002874:Chromosome Mapping; D017362:Cyclic AMP Response Element-Binding Protein; D004260:DNA Repair; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D016678:Genome; D006801:Humans; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000235:genetics*; D019473:Transcription Factors, TFII; D014158:Transcription, Genetic
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D051758:Transcription Factor TFIIH