Test Overview
All coding exons (plus 15 bp upstream and downstream of each coding exon) of the targeted gene(s) are captured, sequenced using NGS and aligned to the human reference genome. A minimum NGS coverage of 20X is achieved for all coding exons +/- 5 bp, and a minimum coverage of 10X an additional 10 bp from +/- 6 bp through +/- 15 bp. A minimum coverage of 10X is achieved for all clinically significant promoter regions. Regions which do not meet these coverage metrics are filled with targeted Sanger Sequencing. Variants in the targeted regions that are of potential clinical significance, based on the ACMG guidelines for interpretation of sequence variants (PMID: 25741868), will be reported. All reported variants of potential clinical significance not meeting the sequencing quality criteria will be confirmed by a different technology.
Analysis for the presence of pathogenic variants in BCAT2, BCKDHA, BCKDHB, DBT, DLD, and PPM1K genes in patients with a phenotype consistent with maple syrup urine disease (MSUD) or abnormal newborn screening results with elevated leucine levels.
Pathogenic variants in the following genes lead to the autosomal recessive MSUD or other disorders with elevated branched-chain amino acids (especially elevated leucine): BCAT2 (MIM: 113530) – Hypervalinemia and hyperleucine-isoleucinemia (HVLI; MIM: 618850); BCKDHA (MIM: 608348) – MSUD type Ia (MIM: 248600; GeneReviews PMID: 20301495); BCKDHB (MIM: 248611) – MSUD type Ib (MIM: 248600; GeneReviews PMID: 20301495); DBT (MIM: 248610) – MSUD type II (MIM: 248600; GeneReviews PMID: 20301495); DLD (MIM: 238331) – Dihydrolipoamide dehydrogenase deficiency (DLDD; MIM: 246900; GeneReviews PMID: 25032271); PPM1K (MIM: 611065) – PPM1K associated MSUD or MSUD mild variant (MSUDMV; MIM: 615135).
Interpretive report provided.
* Reference ranges may change over time. Please refer to the original patient report when evaluating results.
This analysis will not identify variants in the regulatory elements or deep intronic regions not covered in the targeted gene(s) and cannot detect variants in other genes associated with the clinical diagnosis.
Test Details
10 days
Specimen Requirements
Collect specimen in a lavender top tube. Send intact specimen within 24 hours if stored at room temperature or within 5 days if stored refrigerated. Include the patient's family history, pedigree, and ethnicity on the test requisition. Obtaining informed consent from the patient prior to testing is recommended. For a UMHS Request and Consent for Genetic Testing form, contact the MLabs Client Services Center at 800-862-7284 or online at https://mlabs.umich.edu/media/188.
Additional Information
Most insurance carriers require prior authorization for payment. Testing will not begin until insurance prior authorization is received by the MMGL Laboratory, or it has been confirmed that prior authorization is not required. It is the obligation of the ordering health care provider to obtain prior authorization before testing can begin. To obtain BCN prior authorization call Joint Venture Hospital Laboratories (JVHL) at 800-445-4979; for all other insurances, contact the plan directly. By ordering this test the clinician acknowledges that informed consent has been obtained from the patient as required by applicable state or federal laws and the ordering clinician has authorization from the patient permitting MLabs to report the test results to the ordering clinician. Test includes medical geneticist interpretation of results billed as a separate additional charge. This test is not available without interpretation.