CNVs are detected for a subset of the targeted regions using a depth of sequencing coverage approach by applying GC-content normalization. Copy Number Variations (CNVs) are calculated using high quality, de-duplicated and uniquely aligned sequencing reads. Certain sequence changes (SNVs and INDELS) in targeted regions containing repeats, sequences of high homology such as segmental duplications and pseudogenes, as well as regions of high/low GC-content may not be detected. Certain types of genetic abnormalities such as inversions, rearrangements, polyploidy and epigenetic effects are not covered by this test. In cases where two variants are identified in a gene, the test does not distinguish whether these are on one chromosome (in cis) or on different chromosomes (in trans).

Certain sequence changes (SNVs and INDELS) in non-coding regions of selected genes that are of clinical significance are also included in the analysis. Unless otherwise noted, sequence changes (SNVs and INDELS) in the promoter and other non-coding regions are not covered by this assay. Variants that fall outside of the targeted regions are not intended to be detected by this assay. The test aims to detect all variants relevant to the genes listed above by targeting all coding exons, of MANE or/and Canonical transcripts, and 12 bp of adjacent intronic sequence. Seattle (WA): University of Washington, Seattle 1993-2019įH, PH and RAS Kit analyzes 11, 11 and 30 genes and covers Familial Hypercholesterolemia (FH), Pulmonary Hypertension (PH) and RASopathy (RAS) related disorders, respectively.ĪBCA1, ABCG5, ABCG8, APOA5, APOB, APOE, LDLR, LDLRAP1, LIPA, LPL, PCSK9ĪCVRL1, BMPR1B, BMPR2, CAV1, EIF2AK4, ENG, KCNA5, KCNK3, SMAD4, SMAD9, TBX4ĪKT3, BRAF, CBL, CCND2, EPHB4, HRAS, KRAS, LZTR1, MAP2K1, MAP2K2, MRAS, NF1, NF2, NRAS, PIK3CA, PIK3R2, PPP1CB, PTPN11, RAF1, RASA1, RASA2, RIT1, RRAS, SASH1, SHOC2, SMARCB1, SOS1, SOS2, SPRED1, STAMBP 2014, Mol Genet Metab 112(3):210 / Strauss et al., GeneReviews®. Due to the possibility of early detection and therapy with appropriate diet, the prognosis of the disease is favorable.įrazier et al. If positive, the diagnosis can be confirmed by molecular genetics. The patients' urine has a characteristic odor.ĭiagnosis of MSUD is part of newborn screening.

Acute metabolic derangements may occur during catabolic stress. The intermediate form is often associated with developmental delay. The classic form of MSUD manifests in the first weeks of life with nonspecific symptoms (poor drinking, vomiting, comatose states, cerebral edema). BCKDHA codes for the E1a subunit, BCKDHB for E1b, and DBT for the E2 subunit.ĭepending on the variant, a distinction is made betweenĬlinical symptoms appear in the first weeks of life and the early childhood years, depending on the form. The disease is rare, with an incidence of approximately 1:150,000, and is caused by pathogenic variants in the BCKDHA, BCKDHB, and DBT genes, which encode three of the four enzymatically active subunits of the BCKAD complex. The defect results in the accumulation of branched-chain amino acids. This test analyzes genes associated with 421 conditions including the 150 conditions included in QHerit™ Extended carrier screen.Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disease caused by a defect in the alpha-keto acid dehydrogenase complex (BCKAD complex), which mediates the breakdown of the branched-chain amino acids, leucine, isoleucine, and valine. If diagnostic genetic testing is desired, please call Genomic Client Services (GENEINFO) at 866.436.3463 to discuss case with a Quest Genetic Counselor. As this is a screening test, this carrier panel is not intended to be used for diagnostic purposes. Carrier screening aims to identify couples who have an increased risk of having an affected child to facilitate informed reproductive decision-making this large panel may be particularly useful in the pre-conception or fertility setting. This test offers molecular detection by next-generation sequencing (NGS) of variants for specified X-linked and autosomal recessive disorders and allows carrier screening of individuals regardless of ancestry or geographic origin.

Maple syrup urine disease type 1b