title: Multiplex ligation-dependent probe amplification improves diagnostics in spinal muscular atrophy.
abstract: Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by decreased levels of survival motor neuron protein (SMN). In the majority of cases, this decrease is due to absence of the SMN1 gene. Multiplex ligation-dependent probe amplification (MLPA) is a modern quantitative molecular method. Applied in SMA cases, it improves diagnostics by simultaneously identifying the number of copies of several target sequences in the SMN1 gene and in nearby genes. Using MLPA in clinical diagnostics, we have identified a previously unreported, partial deletion of SMN1 (exons 1-6) in two apparently unrelated Swedish families. This mutation would not have been detected by conventional diagnostic methods. This paper illustrates the broad clinical and genetic spectrum of SMA and includes reports of MLPA results and clinical descriptions of a patient with homozygous absence of SMN1 and only one SMN2 (prenatal onset SMA type 1), an asymptomatic woman with five SMN2 (lacking SMN1) and representative patients with SMA types 1, 2 and 3.
authors.affiliation: Department of Clinical Genetics, Sahlgrenska University Hospital/East, Göteborg, Sweden. eva.arkblad@vgregion.se
authors.forename: Eva L
authors.initials: EL
authors.lastname: Arkblad
authors.forename: Niklas
authors.initials: N
authors.lastname: Darin
authors.forename: Kerstin
authors.initials: K
authors.lastname: Berg
authors.forename: Eva
authors.initials: E
authors.lastname: Kimber
authors.forename: Göran
authors.initials: G
authors.lastname: Brandberg
authors.forename: Christopher
authors.initials: C
authors.lastname: Lindberg
authors.forename: Eva
authors.initials: E
authors.lastname: Holmberg
authors.forename: Mar
authors.initials: M
authors.lastname: Tulinius
authors.forename: Margareta
authors.initials: M
authors.lastname: Nordling
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D015342:DNA Probes / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology / Q000379:methods*; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011237:Predictive Value of Tests; D016601:RNA-Binding Proteins / Q000235:genetics*; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D015342:DNA Probes; D009419:Nerve Tissue Proteins; 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