Test Code ISPP Inherited Spastic Paraplegia Gene Panel, Varies

Ordering Guidance

Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.

Customization of this panel and single gene analysis for any gene present on this panel are available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information: To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file.

The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Molecular Genetics: Neurology Patient Information

3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Secondary ID

617610

Useful For

Establishing a molecular diagnosis for patients with hereditary spastic paraplegia

Identifying variants within genes known to be associated with hereditary spastic paraplegia, allowing for predictive testing of at-risk family members

Special Instructions

Method Name

Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

Reporting Name

Spastic Paraplegia Gene Panel

Specimen Type

Varies

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type	Temperature	Time	Special Container
Varies	Varies

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Hereditary spastic paraplegias (HSP) are a group of neurodegenerative disorders characterized by progressive lower extremity weakness and spasticity, both of which can be variable. Other common neurological symptoms include ataxia, cognitive impairment, neuropathy, seizures, and dysarthria. If onset of symptoms occurs in very early childhood, symptoms may be nonprogressive and resemble spastic digenic cerebral palsy. If the onset of symptoms occurs in later childhood or after, symptoms usually progress slowly and steadily.

Clinically HSP are classified in an uncomplicated or pure form and a complicated or complex form. The uncomplicated form presents with progressive lower-extremity spastic weakness, corticospinal tract signs, variable hypertonic urinary bladder disturbance, and disturbance in vibration sense and proprioception. The complicated form is characterized by the impairments present in uncomplicated HSP plus other system involvement or other neurologic findings. Additionally, the complicated form usually follows an autosomal recessive inheritance pattern, while the uncomplicated form predominantly follows an autosomal dominant inheritance pattern.

Given HSP are a heterogeneous group of disorders, multigene panels can be an efficient and cost-effective way to establish a molecular diagnosis for symptomatic individuals.

Reference Values

An interpretive report will be provided.

Interpretation

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Method Description

Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletion-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed.

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. See Targeted Genes and Methodology Details for Inherited Spastic Paraplegia Gene Panel for details regarding the targeted genes analyzed for each test and specific gene regions not routinely covered.(Unpublished Mayo method)

Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

Genes analyzed: ABCD1, ACO2, AFG3L2, ALDH18A1, AMPD2, AP4B1, AP4E1, AP4M1, AP4S1, AP5Z1, APOPT1 (COA8), ARG1, ARL6IP1, ASNS, ATL1, AUH, B4GALNT1, BICD2, BOLA3, BSCL2, C12orf65 (MTRFR), COQ7, CPT1C, CTC1, CTSD, CYP27A1, CYP2U1, CYP7B1, DARS1, DARS2, DDHD1, DDHD2, DLD, EARS2, ENTPD1, ERLIN1, ERLIN2, EXOSC3, FA2H, FAR1, FARS2, FUCA1, FXN, GALC, GBA2, GBE1, GJC2, GLB1, GM2A, GPT2, HACE1, HEXA, HIBCH, HSPD1, HTRA1, IBA57, IFIH1, IRF2BPL, ISCA2, KDM5C, KIDINS220, KIF1A, KIF5A, L1CAM, L2HGDH, LYRM7, MAG, MARS2, MED17, MTFMT, NIPA1, NT5C2, NUBPL, OPA3, PANK2, PDHX, PEX16, PGAP1, PLA2G6, PLP1, PNP, PNPLA6, PNPLA8, PRF1, PRUNE1, PSAP, PYCR2, RAB18, RAB3GAP1, RAB3GAP2, RARS1, REEP1, REEP2, RNASEH2A, RNASEH2B, RNASEH2C, RTN2, SACS, SAMHD1, SDHAF1, SERAC1, SLC12A6, SLC16A2, SLC19A3, SLC33A1, SLC6A8, SOX2, SPART, SPAST, SPG11, SPG21, SPG7, SPTAN1, SUMF1, TACO1, TBC1D20, TECPR2, TFG, TREX1, TTC19, TYROBP, UBAP1, UBQLN2, VAMP1, VPS13D, WASHC5, ZFYVE26, and ZFYVE27

Day(s) Performed