Spinal Muscular Atrophy – I, II and III

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SPINAL MUSCULAR ATROPHY - I, II AND III

Gene Symbol: SMN1

Chromosomal Locus: 5q13.1
 
Protein: Survival Motor Neuron 1, telomeric
 
Pseudonyms: SMA, types I-IV, Werdnig-Hoffmann disease, Kugelberg-Welander disease
 
TURNAROUND TIME: 8 days
   
TESTING METHODOLOGY: Detection of a homozygous deletion of SMN1 exon 7 and 8 by polymerase chain reaction (PCR) & restriction enzyme digestion.
 
SPECIMEN REQUIREMENTS:
  • Collect: Prefer two 5ml whole blood EDTA (lavender top) tube.
  • Min. Collection: 0.7 ml whole blood EDTA.
  • Transport: blood EDTA at Room Temp shipped regular next day air (No Saturday delivery; store specimen at 4°C and ship Monday).
  • Stability: Ambient: up to 7 days; Refrigerated: 2 weeks. Frozen: unacceptable
  • Unacceptable Conditions: Serum. Frozen or severely hemolyzed blood. Clotted blood.
  • Prenatal testing: Direct: 5ml direct unspun amniotic fluid or 15mg CVS tissue with a backup flask growing. Culture: confluent T25 flask. Maternal blood sample is required for maternal cell contamination studies.
A Molecular Genetics Laboratory Test Requisition must accompany the specimen. Contact the Molecular Laboratory at 918-502-1721 to obtain further information.
 
*Note: Counseling and informed consent are recommended for genetic testing. A consent form is available as a resource but not required.
 
INTERPRETATIVE DATA:
 
Incidence: 1 in 10,000 in the USA
 
Inheritance: Autosomal recessive; 2% of cases result from a de novo mutation on one of the alleles.
 
Disease Characteristics: Muscle weakness and atrophy due to a loss of motor nerves in the spinal cord and brain stem. Onset of disease ranges from before birth to young adulthood. Weakness is almost always symmetric and progressive, leading to paralysis of the limbs and trunk. SMA, type I (Werdnig-Hoffman syndrome) strikes within the first 6 months of life. Most children with SMAI die before reaching 2 years of age due to respiratory failure.
 
Molecular Genetic Mechanism: Homozygous deletion of exon 7 of the SMN1 gene is responsible for 95-98% of all cases of SMA. Most case with a deletion will have a deletion of exon 8 as well.
 
 
Clinical Sensitivity: 95-98% **
 
Analytic Sensitivity: 99%*
 
Test Limitations: *This assay will not detect SMA carrier status. ** Mutations other than the homozygous deletion of exons 7 or 8 will not be detected (2-5%). Rare diagnostic errors can occur due to primer or probe site mutations or rare polymorphisms.
 
INDICATIONS FOR USE:
  • Confirmation of the diagnosis of SMA.
  • Individuals at risk who wish prenatal diagnosis.
ADDITIONAL RESOURCES: