Prenatal Noonan Syndrome
81404; 81405; 81406 (x6); 81479
Genes tested: BRAF, HRAS, KRAS, MAP2K1, MAP2K2, PTPN11, RAF1, and SOS1. This test covers all coding nucleotides plus at least two and typically 10 flanking intronic nucleotides upstream and downstream of each coding exon, covering the conserved donor and acceptor splice sites, typically 10 flanking nucleotides in the 5′ and 3′ UTR. Testing covers exon 2 of SHOC2.
Please call CMBP genetic coordinators at 800-345-4363 prior to submitting a fetal sample. Test orders must include attestation that the provider has the patient's informed consent for genetic testing. See sample physician office consent form: Consent for Genetic Testing. In the case of a family test (ie, known mutation), family tests will only be accepted from family members of index cases tested at LabCorp. Please order test 451385 to submit family testing for Noonan syndrome.
Amniotic fluid, chorionic villus sample (CVS), cultured amniocytes, cultured villi. (Cultured cells are required for testing. Direct specimen can be submitted, but a culture fee may be included.) Submission of maternal blood is required for analysis of Maternal Cell Contamination (511402), which should be ordered on a separate test request form.
Amniotic fluid: 20 cc, CVS: 20 mg, or amniotic fluid and CVS culture: Two confluent flasks
Sterile plastic conical tube or two confluent T-25 flasks for fetal testing
Maintain specimen at room temperature or refrigerate at 4°C.
Causes for Rejection
Frozen specimen; hemolysis; quantity not sufficient for analysis; improper container
Prenatal diagnosis for at-risk pregnancies when a parent is affected or when abnormalities are seen on fetal ultrasound. Noonan syndrome and Noonan-like syndromes tend to be predominantly associated with different genes or different variants within the same genes. Clinical overlap of the various syndromes is explained by the fact that all of these genes code for components of the same intracellular signaling pathway, namely the Ras/MAPK signaling cascade.
Genetic testing for Noonan syndrome and related disorders may:
- Establish or confirm a clinical diagnosis of Noonan syndrome, LEOPARD syndrome, Costello syndrome, or cardiofaciocutaneous syndrome.
- Identify previously undiagnosed parents, siblings, and other relatives of patients with Noonan syndrome or LEOPARD syndrome.
- Facilitate appropriate genetic counseling for family members.
This analysis does not rule out: germline mosaicism, the presence of large chromosomal aberrations including deletions, insertions, and rearrangements, mutations in regions or genes not included in this test, and possible inter/intragenic interactions between sequence variants. False positives or negative results may occur for reasons that include: genetic variants, blood transfusions, bone marrow transplantation, mislabeled specimens or erroneous representation of family relationships.
Mutation analysis is performed using the Agilent Sure Select XT® enrichment method and the Illumina® next-generation sequencing (NGS) platform. Regions of interest include all exons and splice junctions for each gene and limited regions for the following: SHOC2 (exon 2), APOB (556bp of exon 26), and AKAP9 (exon 18). Sequencing reads are aligned with the hg19 build of the human genome reference sequence. Analytical sensitivity is based on the depth of coverage across the regions of the interest and is provided separately for each gene. Greater than 98% of target bases are synonymous variants not previously recorded at ≥20x coverage. Sanger sequencing is used to confirm mutation identity and analyze regions with low coverage. Variants are reported using numbering and nomenclature recommended by the Human Genome Variation Society. Variants known to be benign and synonymous variants not previously recorded in our internal variant databases are not reported.
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