Test code: 7181

Pan-Ethnic Carrier Screen: Mutation and SMA Analysis
Test Code: 7181
Turnaround time: 3 weeks

CONDITION DESCRIPTION

This test may be ordered for males and females.

Test components:

  • Carrier screening for recessive conditions by NGS mutation analysis
  • Carrier screening for spinal muscular atrophy (SMA)

Carrier screening for recessive conditions by NGS mutation analysis
This component of the Pan-Ethnic Carrier Screen tests for 690 pathogenic variants in 136 genes causing autosomal recessive conditions. It is the most extensive carrier screen to date and includes conditions of mobility, developmental delay, visual impairment, hearing loss, intellectual disability, skin irregularities, joint and bone disorders, abnormalities of the nervous system, and numerous metabolic syndromes. None of these conditions has a cure, but some can be well managed with diet or medication (e.g. PKU or biotinidase deficiency). Many of these conditions, however, can result in a shortened lifespan or require continued medical care (e.g. Tay-Sachs disease or cystic fibrosis).

Carrier screening for spinal muscular atrophy (SMA)
Spinal muscular atrophy (SMA) is the second most common lethal, autosomal recessive disorder in Caucasians, with an incidence of approximately 1/10,000 and a carrier frequency of 1/50. SMA is characterized by anterior horn cell degeneration which causes a symmetrical muscle weakness and wasting. SMN1 is deleted in about 95% of individuals with SMA. This carrier assay tests for the common SMN1 deletion only; other pathogenic variants will not be detected.

Approximately 5-8% of carrier individuals will have a normal SMN1 copy number of two, but both copies will be on the same chromosome (in cis) with a deletion on the second chromosome. This assay will not detect these carrier individuals. This assay will not report SMN2 copy number.

Although a positive test result should not affect the health of the individual, he/she could be at a 25% risk for passing that condition on to his/her children depending on the carrier status of the partner. In addition to the specific pathogenic variants identified by the panel, Emory Genetics Laboratory also offers single-gene, full gene sequencing for genes on the panel, which can be utilized to screen partners of positive carriers. Knowing about these risks ahead of time can help couples make decisions about testing options prior to and during pregnancy, and can help healthcare providers be more readily prepared to offer appropriate follow-up care at delivery. While the specific risks will vary, the Pan-Ethnic Carrier Screen is appropriate for individuals of all ethnicities.

GENES
ABCC8, ACADM, ACADS, ACADVL, ACAT1, AGA, AGL, AGXT, AIRE, ALDH3A2, ALDOB, ALPL, ARSA, ARSB, ASL, ASPA, ASS1, ATM, ATP7B, BBS1, BBS10, BCKDHA, BCKDHB, BCS1L, BLM, BTD, CAPN3, CBS, CFTR, CLN3, CLN5, CLN8, CLRN1, CNGB3, CPT1A, CPT2, CTNS, CTSC, CTSK, CYP1B1, CYP21A2, DBT, DHCR7, DLD, DPYD, EDAR, F11, FAH, FANCC, FH, FKTN, G6PC, GAA, GALC, GALNS, GALT, GBA, GCDH, GHRHR, GJB2, GJB6, GLB1, GNE, GNPTAB, GP1BB, GP9, GRHPR, GUSB, HADHA, HBB, HEXA, HEXB, HFE, HMOX1, HSD17B4, IDUA, IKBKAP, IVD, LAMA3, LAMB3, LAMC2, LIPH, MAN2B1, MCOLN1, MEFV, MLC1, MMAA, MMAB, MMACHC, MPI, MUT, NAGLU, NBN, NEB, NLRP7, NPC1, NPC2, NPHS1, NPHS2, OPA3, PAH, PANK2, PCDH15, PEX1, PEX7, PKHD1, PMM2, POMGNT1, PPT1, PROP1, PYGM, RMRP, SACS, SERPINA1, SGCA, SGCB, SGCG, SGSH, SLC12A6, SLC17A5, SLC19A2, SLC22A5, SLC26A2, SLC26A4, SLC37A4, SMN1, SMPD1, TH, TMEM216, TPP1, TTC37, TTPA, TYR, VPS13B, WISP3, WRN

INDICATIONS

This test is indicated for:

  • Individuals or couples seeking to assess reproductive risk for a variety of conditions.
  • Individuals or couples of high-risk ethnic groups or backgrounds.

METHODOLOGY
Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient’s genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not mean to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient’s gene sequences are then compared to a standard reference sequence. Only known pathogenic variants will be reported.

Spinal Muscular Atrophy (SMA) Testing: SMN1 gene deletions were quantified by multiplex ligation polymerase chain reaction amplification (MLPA) of exons 7 and 8. Gene dosage ratios of SMN1 are calculated relative to the average of 16 reference loci and are expressed as gene dosage, and/or copy number. Diploid gene dose or 2 copies of SMN1 indicates normal (not affected) status, 1x gene dosage or 1 copy of the SMN1 gene most likely indicates carrier status and deletions (less than 0.1x) of SMN1 or 0 copies of the SMN1 gene designates affected status. This carrier assay tests for the common SMN1 deletion only; other pathogenic variants will not be detected. SMN2 copy number is not assessed.

DETECTION
Next Generation Sequencing: Clinical Sensitivity: Pathogenic variants in regions other than the targeted area, including the promoter region, some mutations in the introns and other regulatory element mutations, cannot be detected by this analysis. Large deletions/ duplications will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient’s clinical/biochemical phenotype.

Analytical Sensitivity: ~99%.

For Spinal Muscular Atrophy (SMA) Testing: Deletions of the SMN1 gene are found in approximately 95% of individuals with SMA. This carrier assay tests for the common SMN1 deletion only; other pathogenic variants will not be detected. SMN2 copy number is not assessed.

SPECIMEN REQUIREMENTS
Submit only 1 of the following specimen types

Type: Saliva
Specimen Requirements:
OrageneTM Saliva Collection Kit (available from CEN4GEN).

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) tube:
Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml.

Specimen Collection and Shipping: Ship sample at room temperature with overnight delivery.

Type: Isolated DNA
Specimen Requirements:
In microtainer: 60 ug

Isolation using the QiagenTM Puregene kit for DNA extraction is recommended.

Specimen Collection and Shipping: Refrigerate until time of shipment in 100 ng/ul of TE buffer. Ship sample at room temperature with overnight delivery.

RELATED TESTS

  • Pan-Ethnic Carrier Screen: Mutation Analysis
  • Pan-Ethnic Carrier Screen: Mutation, Including X-Linked Conditions (With Fragile X Repeat Analysis)
  • Pan-Ethnic Carrier Screen: Mutation Analysis, Including X-Linked Conditions (With Fragile X Repeat Analysis), and SMA Analysis
  • Ashkenazi Jewish Carrier Screen