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.
- Patient Preparation
- Fetal Specimen: Two T-25 flasks at 80 percent confluency of cultured amniocytes or CVS. If the client is unable to culture amniocytes, this can be arranged by contacting ARUP Client Services at (800) 522-2787.
AND Maternal Specimen: Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).
- Specimen Preparation
- Cultured Amniocytes or Cultured CVS: Fill flasks with culture media. Transport two T-25 flasks at 80 percent confluency of cultured amniocytes or cultured CVS. Backup cultures must be retained at the client's institution until testing is complete.
Maternal Specimen: Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Amniotic Fluid: Room temperature.
Cultured Fetal Cells: CRITICAL ROOM TEMPERATURE. Must be received within 48 hours of shipment due to viability of cells.
Maternal Specimen: Room temperature.
- Unacceptable Conditions
- Maternal specimen is recommended for proper test interpretation. Order Maternal Cell Contamination. In some cases, samples from additional relatives may be necessary for optimal interpretation; 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.
- Fetal Specimen: Ambient: 48 hours; Refrigerated: Unacceptable; Frozen: Unacceptable
Maternal Specimen: Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
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 (zero) functioning copies of the SMN1 gene that produces survival motor neuron protein; most (95 percent) have homozygous loss of SMN1 due to deletion or gene conversion, while some (5 percent) have a sequence variant in one remaining copy of SMN1. 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, but phenotype cannot be predicted with certainty.
Inheritance: Autosomal recessive
Cause: Pathogenic mutations 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 in individuals affected with SMA.
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 mutations, and deep intronic mutations 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.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|0050548||Maternal Contamination Study Fetal Spec||59266-7|
|0050612||Maternal Contam Study, Maternal Spec||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|
|2013445||SMA Copy Number, Specimen|
|2013446||SMA Copy Number, Interp|