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
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).
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.
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.
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
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.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.
Laboratory Developed Test (LDT)
Note: Maternal specimens are recommended as controls for proper test interpretation. Order Maternal Cell Contamination (ARUP test code 0050608) on the maternal 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||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|