title: Population screening and cascade testing for carriers of SMA.
abstract: Spinal muscular atrophy (SMA) is one of the most common autosomal-recessive diseases, caused by absence of both copies of the survival motor neuron 1 (SMN1) gene. Identification of SMA carriers has important implications for individuals with a family history and the general population. SMA carriers are completely healthy and most are unaware of their carrier status until they have an affected child. A total of 422 individuals have been studied to identify SMA carriers. This cohort included 117 parents of children homozygously deleted for SMN1 (94% were carriers and 6% had two copies of SMN1; of these individuals, two in seven had the '2+0' genotype, two in seven were normal but had children carrying a de novo deletion and three in seven were unresolved), 158 individuals with a significant family history of SMA (47% had one copy, 49% had two copies and 4% had three copies of SMN1) and 146 individuals with no family history of SMA (90% had two copies, 2% had one copy and 8% had three copies of SMN1). The SMA carrier frequency in the Australian population appears to be 1/49 and the frequency of two-copy SMN1 alleles and de novo deletion mutations are both at least 1.7%. A multimodal approach involving quantitative analysis, linkage analysis and genetic risk assessment (GRA), facilitates the resolution of SMA carrier status in individuals with a family history as well as individuals of the general population, providing couples with better choices in their family planning.
authors: Molecular Genetics Laboratory, Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
authors: Melanie
authors: M
authors: Smith
authors: Vanessa
authors: V
authors: Calabro
authors: Belinda
authors: B
authors: Chong
authors: Nicole
authors: N
authors: Gardiner
authors: Shannon
authors: S
authors: Cowie
authors: Desirée
authors: D
authors: du Sart
mesh_terms: D001315:Australia / Q000453:epidemiology; D015331:Cohort Studies; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D006580:Genetic Carrier Screening / Q000379:methods*; D008040:Genetic Linkage; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis* / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009520:New Zealand / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D016601:RNA-Binding Proteins / Q000235:genetics*; 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