Multiplex ligation-dependent probe amplification improves diagnostics in spinal muscular atrophy

• 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.

Nyckelord

Adolescent

Adult

Child

Cyclic AMP Response Element-Binding Protein

genetics

DNA Mutational Analysis

methods

DNA Probes

genetics

Exons

genetics

Female

Gene Deletion

Gene Dosage

genetics

Genetic Predisposition to Disease

genetics

Genotype

Humans

Infant

Infant

Newborn

Inheritance Patterns

genetics

Male

Middle Aged

Molecular Biology

methods

Muscular Atrophy

Spinal

diagnosis

genetics

physiopathology

Mutation

genetics

Nerve Tissue Proteins

genetics

Predictive Value of Tests

RNA-Binding Proteins

genetics

MLPA

MEDICINE

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)