Noonan Syndrome – Tiered Molecular Testing
|Gene Names||Tier 1: Full sequencing of PTPN11
Tier 2: Full sequencing of SOS1
Tier 3: Full sequencing of RAF1 and KRAS and SHOC2 – S2G mutation
Tier 4: Full sequencing of BRAF, MAP2K1 and NRAS
Full Panel: Tiers 1, 2, 3, & 4
|Clinical info||Noonan syndrome is characterized by short stature, developmental delay, characteristic facial features, a webbed or broad neck, low-set nipples and chest abnormalities. Heart defects are present in up to 80% of patients and mild intellectual disability may be a feature in approximately 1/3 of patients.|
|Indications||Tiers may be ordered separately or can be run as a concurrent panel. If you are requesting multiple tiers, but would like each run separately, please indicate the order if which testing should be done. Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutation within a family to allow for carrier testing and prenatal diagnosis.|
|Associated Tests||The features of Noonan syndrome are often found to overlap with those of Costello syndrome and cardio-facio-cutaneous (CFC) syndrome, so tiered analyses for these conditions is also available. In addition, each of these genes is included in the NGS RASopathy Panel.|
|Detection||PTPN11 mutations are responsible for approximately 50% of Noonan syndrome cases. Mutations in SOS1 have been identified in approximately 15-20% of those without a PTPN11 mutation. RAF1 and KRAS are each responsible for approximately 5% of individuals with Noonan syndrome. Patients with Noonan-like syndrome with loose anagen hair have recently been identified as having a S2G mutation in SHOC2.|
|Specimen Requirements||5 to 10 ml of peripheral blood collected in an EDTA (lavender top) Vacutainer tube is preferred. The minimal blood needed for reliable DNA isolation is 3 ml|
|Transport||The specimen should be kept at room temperature and delivered via overnight shipping. FedEx is preferred. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.|
|Turnaround time||Tier 1: 6 weeks
Tier 2: 6 weeks
Tier 3: 6 weeks
Tier 4: 6 weeks
|Prenatal testing||Prenatal diagnosis is available if the familial mutation is known. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.|
Tier 1: $1000
$700 for deletion/duplication analysis for single gene OR $1200 for deletion/duplication analysis of all genes on panel.
Prenatal diagnosis for a known mutation is $1000. Please contact the lab for more information.
Molecular Diagnostic Lab
The Molecular Diagnostic Lab offers DNA analysis for many genetic disorders via gene sequencing, targeted mutation analysis, MLPA deletion/duplication testing, trinucleotide repeat analysis and next generation sequencing panels.