Spinal Muscular Atrophy (SMA) Copy Number Analysis (Temporary Delay as of 11/20/20 no referral available)
Confirm a suspected diagnosis of spinal muscular atrophy (SMA) and quantify SMN2 copy number for treatment purposes in affected individuals. Use for prenatal or preconception carrier screening for SMA in the general population, carrier screening for the reproductive partner of a known SMA carrier, and carrier screening for parents of a child with a deletion of the SMN1 gene or other family history of SMA.
Multiplex Ligation-dependent Probe Amplification
Within 14 days
Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).
Transport 3 mL whole blood. (Min: 2 mL)
Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months.
Background information for Spinal Muscular Atrophy (SMA) Copy Number Analysis
Characteristics: Spinal muscular atrophy (SMA) is the most common lethal genetic disease in children, and is characterized by progressive muscle weakness due to degeneration of the lower motor neurons. Onset ranges from before birth to adulthood and severity is highly variable. Individuals with SMA have no functioning copies of the SMN1 gene. Most (95 percent) have homozygous loss of SMN1 due to deletion or gene conversion, while a minority (5 percent) have a deletion of SMN1 on one chromosome and a SMN1 sequence variant on the other. The SMN2 gene, adjacent and highly homologous to SMN1, produces lower levels of survival motor neuron protein compared to SMN1. Disease severity has been shown to be modified by SMN2 gene copy number in some cases, though phenotype cannot be predicted with certainty. An SMN1 variant, c.*3+80T>G (rs143838139), that is part of a haplotype associated with SMN1 duplication in silent carriers (2 copies of SMN1 on one chromosome and no copies on the other), particularly in Ashkenazi Jews, increases the likelihood that 2 copies of SMN1 are on the same chromosome.
Inheritance: Autosomal recessive.
Cause: Pathogenic variants in the SMN1 gene.
Variants Tested: For copy number: SMN1 (NM_000344.3) exon 7 c.840C and exon 8 c.*239G, and SMN2 (NM_017411.3) exon 7 c.840T. For haplotype associated with SMN1 duplication (silent carriers): SMN1 c.*3+80T>G (rs143838139).
Clinical sensitivity: 95-98 percent in individuals affected with SMA. Detection rate for carrier screening is 90 percent in African Americans, 93 percent in Ashkenazi Jewish, 93 percent in Asians, 95 percent in Caucasians, and 93 percent in Hispanics.
Methodology: Multiplex probe ligation-dependent amplification (MLPA) to detect SMN1 and SMN2 copy number and presence or absence of the SMN1 linked variant c.*3+80T>G (rs143838139).
Analytical sensitivity and specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Single base pair substitutions, small deletions/duplications, regulatory region mutations, and deep intronic mutations will not be detected. This test is unable to determine chromosomal phase of SMN1 or SMN2 copies. Even if the linked variant associated with SMN1 duplication is detected, the test cannot definitively differentiate between 1+ copies of SMN1 on each chromosome from 2+ copies of SMN1 on one chromosome and none on the other (silent carriers).
Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.
Laboratory Developed Test (LDT)
|Component Test Code*||Component Chart Name||LOINC|
|2013437||SMA Copy Number, Specimen||31208-2|
|2013438||SMA Copy Number, Symptoms||75325-1|
|2013439||SMA Copy Number, SMN1 Copies||35462-1|
|2013440||SMA Copy Number, SMN2 Copies||54449-4|
|2013441||SMA Copy Number, Linked Variant||82155-3|
|2013442||SMA Copy Number, Int||49857-6|
- Spinal Muscular Atrophy