title: Molecular analysis of SMN, NAIP and P44 genes of SMA patients and their families.
abstract: Mutations of the telomeric survival motor neuron gene (SMN1) are related to spinal muscular atrophy (SMA). However, no phenotype-genotype correlation has been observed since the SMN1 gene is lacking in the majority of patients affected with either the severe form (type I) or the milder forms (types II and III). Here, we analyze the SMN, NAIP and P44 genes in 132 Chinese SMA patients and their families. At least three types of normal allele, and four types of mutant allele were found in this study. The combination of one normal allele with one mutant allele resulted in carriers of different types, and the combination of different mutant alleles accounted for the different genotypes among different types of SMA. Deletions of mutant alleles can be further subgrouped into four types, which includes involving SMN1, SMN1 and NAIP(T) (telomeric portion of NAIP gene), SMN1 and NAIP(T) and P44(T) (telomeric portion of P44 gene), and SMN1 and SMN2 (centromeric portion of SMN gene). Some of the severe (type I) SMA cases correlated with the extent of deletions in the SMN, NAIP and P44 genes or the dosage of SMN gene when both SMN1 and SMN2 are deleted. We also found two novel point mutations, an A insertion at codon 8 (AGT-->AAGT) and an A substitution at codon 228 (TTA-->TAA).
authors.affiliation: Department of Medical Research, China Medical College Hospital, 2 Yuh Der Road, Taichung, Taiwan.
authors.forename: C H
authors.initials: CH
authors.lastname: Tsai
authors.forename: Y J
authors.initials: YJ
authors.lastname: Jong
authors.forename: C J
authors.initials: CJ
authors.lastname: Hu
authors.forename: C M
authors.initials: CM
authors.lastname: Chen
authors.forename: M C
authors.initials: MC
authors.lastname: Shih
authors.forename: C P
authors.initials: CP
authors.lastname: Chang
authors.forename: J G
authors.initials: JG
authors.lastname: Chang
mesh_terms: D000870:Anterior Horn Cells / Q000473:pathology / Q000503:physiopathology*; D002678:Chimera / Q000235:genetics; D002681:China; D017362:Cyclic AMP Response Element-Binding Protein; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D017353:Gene Deletion; D005787:Gene Frequency / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051616:Neuronal Apoptosis-Inhibitory Protein; D010375:Pedigree; D010448:Peptide Initiation Factors / Q000235:genetics*; D010641:Phenotype; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics*; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein; D016615:Telomere / Q000235:genetics
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; C496800:NAIP protein, human; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein