Prenatal diagnostic testing for spinal muscular atrophy (SMA) when both parents carry a deletion of SMN1 or have a previous child with SMA caused by a deletion of SMN1.
Multiplex Ligation-dependent Probe Amplification
Within 10 days
New York DOH Approval Status
Cultured amniocytes or Cultured CVS
AND Maternal Whole Blood Specimen: Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).
Cultured Amniocytes or Cultured CVS: Transfer cultured amniocytes or cultured CVS to two T-25 flasks at 80 percent confluence (Min: one T-25 flask at 80% confluence). Backup cultures must be retained at the client's institution until testing is complete. If the client is unable to culture amniocytes or CVS, this can be arranged by contacting ARUP Client Services at (800) 522-2787. Please contact an ARUP genetic counselor at (800) 242-2787 ext. 2141 prior to test submission.
Maternal Whole Blood Specimen: Transport 2 mL whole blood. (Min: 1 mL)
Cultured Amniocytes or Cultured CVS: CRITICAL ROOM TEMPERATURE. Must be received within 48 hours of collection due to viability of cells.
Maternal Whole Blood Specimen: Room temperature.
Please contact an ARUP genetic counselor at 800-242-2787 x2141 prior to sample submission. Patient History Form is available on the ARUP Web site or by contacting ARUP Client Services at (800) 522-2787.
Cultured Amniocytes or Cultured CVS: Room temperature: 48 hours; Refrigerated: Unacceptable; Frozen: Unacceptable
Maternal Whole Blood Specimen: Room Temperature: 7 days; Refrigerated: 1 month; Frozen: Unacceptable
Background information for Spinal Muscular Atrophy (SMA) Copy Number Analysis, Fetal
Characteristics: Spinal muscular atrophy (SMA) is the most common lethal genetic disease in children. It is characterized by progressive muscle atrophy and weakness, poor weight gain, restrictive lung disease, scoliosis, and joint contractures due to degeneration of lower motor neurons and brain stem nuclei. Onset ranges from before birth to young adulthood and severity is highly variable. Individuals with SMA have no functional copies of the SMN1 gene either due to homozygous loss of SMN1 from deletion or gene conversion (95 percent) or loss of one SMN1 gene and a pathogenic sequence variant in the other (5 percent). The SMN2 gene produces a small amount of functional survival motor neuron protein compared to SMN1. An increased number of SMN2 gene copies may reduce disease severity but phenotype cannot be predicted with certainty.
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.
Clinical sensitivity: 95-98 percent.
Methodology: Multiplex probe ligation-dependent amplification (MLPA).
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 and deep intronic variants will not be detected. This test is unable to determine chromosomal phase of SMN1 or SMN2 copies.
For quality assurance purposes, ARUP Laboratories will confirm the above result at no charge following delivery. Order Confirmation of Fetal Testing and include a copy of the original fetal report (or the mother's name and date of birth) with the test submission. Please contact an ARUP genetic counselor at (800) 242-2787 extension 2141 prior to specimen submission.
This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test was performed in a CLIA certified laboratory and is intended for clinical purposes.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
Laboratory Developed Test (LDT)
Note: Maternal specimens are recommended as controls for proper test interpretation. Submit maternal blood specimen for Maternal Cell Contamination in addition to fetal specimen.
81329; 81265 Fetal Cell Contamination (FCC)
|Component Test Code*||Component Chart Name||LOINC|
|0050548||Maternal Contamination Study Fetal Spec||59266-7|
|0050612||Maternal Contam Study, Maternal Spec||66746-9|
|2013438||SMA Copy Number, Symptoms||75325-1|
|2013439||SMA Copy Number, SMN1 Copies||35462-1|
|2013440||SMA Copy Number, SMN2 Copies||54449-4|
|2013445||SMA Copy Number, Specimen||66746-9|
|2013446||SMA Copy Number, Interp||35462-1|