title: Characterization of survival motor neuron (SMNT) gene deletions in asymptomatic carriers of spinal muscular atrophy.
abstract: Previous reports have established that the telomeric copy of the survival motor neuron (SMNT) gene and the intact copy of the neuronal apoptosis inhibitory protein (NAIP) gene are preferentially deleted in patients with spinal muscular atrophy (SMA). Although deletions or mutations in the SMNT gene are most highly correlated with SMA, it is not clear to what extent NAIP or other genes influence the SMA phenotype, or whether a small fraction of SMA patients actually have functional copies of both SMNT and NAIP. To evaluate further the part of SMNT in the development of SMA, we analyzed 280 asymptomatic SMA family members for the presence or absence of SMNT exons 7 and 8. We report the following observations: (i) 4% of the sample harbored a polymorphic variant of SMNT exon 7 that looks like a homozygous deletion; (ii) approximately 1% of the parents are homozygously deleted for both exons 7 and 8; (iii) one asymptomatic parent lacking both copies of SMNT exons 7 and 8 displays a 'subclinical phenotype' characterized by mild neurogenic pathology; (iv) another asymptomatic parent lacking both SMNT exons showed no signs of motor neuron disorder by clinical and neurodiagnostic analyses. The demonstration of polymorphic variants of exon 7 that masquerade as homozygous nulls, and the identification of SMA parents who harbor two disease alleles, serve as a caution to those conducting prenatal tests with these markers.
authors.affiliation: Department of Genetics and Development, College of Physicians and Surgeons at Columbia University, New York, NY 10032, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: T A
authors.initials: TA
authors.lastname: Carter
authors.forename: B M
authors.initials: BM
authors.lastname: Ross
authors.forename: M K
authors.initials: MK
authors.lastname: Dominski
authors.forename: C A
authors.initials: CA
authors.lastname: Bellcross
authors.forename: G K
authors.initials: GK
authors.lastname: Penchaszadeh
authors.forename: T L
authors.initials: TL
authors.lastname: Munsat
authors.forename: T C
authors.initials: TC
authors.lastname: Gilliam
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002895:Chromosomes, Human, Pair 5; D017362:Cyclic AMP Response Element-Binding Protein; D004576:Electromyography; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein
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