Non-Syndromic Monogenic Obesity Panel
Summary and Pricing
Test MethodSequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
|Test Code||Test Copy Genes||Gene CPT Codes Copy CPT Codes|
|15183||KSR2||81479,81479||Order Options and Pricing|
|Test Code||Test Copy Genes||Panel CPT Code||Gene CPT Codes Copy CPT Code||Base Price|
|15183||Genes x (11)||81479||81403, 81406, 81479||$640||Order Options and Pricing|
We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available.
This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
18 days on average for standard orders or 14 days on average for STAT orders.
Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
Obesity is defined as an increase in fat mass that is sufficient to adversely affect health and reduce longevity (Fontaine et al. 2003. PubMed ID: 12517229). Clinically, adults with a body-mass index (BMI) greater than 30 kg/m2 are considered obese. BMI is a multifactorial trait that is usually influenced by multiple genes (Gusev et al. 2014. PubMed ID: 25439723), as well as environmental and lifestyle factors. However, in some cases obesity is inherited by a monogenetic mechanism due to pathogenic variants in a single gene.
The non-syndromic form of monogenic obesity is a group of single gene disorders with obesity as an isolated or predominant feature. The obesity phenotype in these patients is typically severe and early-onset. Infants experience rapid weight gain in the first year of life and reach a BMI > 3 standard deviations above the mean. Associated features include hyperphagia, increased linear growth, delayed puberty, preserved reproductive function, hypocortisolemia and hyperinsulinemia (Albuquerque et al. 2015. PubMed ID: 25749980; Pigeyre et al. 2016. PubMed ID: 27154742)
The largest genetic contributors to non-syndromic obesity include genes expressed in the hypothalamus that control energy balance via the leptin-melanocortin signaling pathway (LEP, LEPR, MC4R, POMC, PCSK1, SH2B1, and SIM1). MC4R deficiency is the most prevalent of these disorders, affecting up to 1 in 2,000 individuals (Orphanet). Obesity due to pathogenic MC4R variants is inherited by a semidominant mechanism; the phenotype is severe and fully penetrant in homozygotes or compound heterozygotes, and milder with incomplete penetrance in heterozygotes. POMC and PCSK1 have similar inheritance properties. LEP and LEPR cause autosomal recessive obesity; SH2B1 and SIM1 cause obesity with autosomal dominant inheritance.
Additional genes mediate neuron differentiation and proliferation via tyrosine kinase signaling in the brain, apparently unrelated to the leptin pathway (NTRK2 and KSR2; Pigeyre et al. 2016. PubMed ID: 27154742). NTRK2 and KSR2-related obesity is autosomal dominant.
Finally, UCP3 and NR0B2 are involved in energy utilization in peripheral tissues such as skeletal muscle and liver (Millet et al. 1997. PubMed ID: 9389729; Lu et al. 2000. PubMed ID: 11030331). Pathogenic variants in these genes may cause obesity with autosomal dominant or recessive inheritance.
The genes included on this panel account for all known causes of monogenic non-syndromic obesity due to pathogenic sequence alterations. Pathogenic variants include missense and nonsense changes as well as small and large insertions/deletions (Human Gene Mutation Database). In some cases multifactorial inheritance has been proposed, however, at this time the number of cases is too small to clearly define these variants (Pigeyre et al. 2016. PubMed ID: 27154742).
Clinical Sensitivity - Sequencing with CNV PG-Select
It is difficult to estimate the clinical sensitivity of this test given the significant contribution of environment to obesity. For the MC4R gene alone, the prevalence of pathogenic variants is predicted to be 0.5 - 1% in obese adults and up to 6% in severely obese children (Farooqi and O'Rahilly. 2005. PubMed ID: 15660521; Farooqi et al. 2003. PubMed ID: 12646665). This range in prevalence demonstrates that sensitivity is strongly influenced by the severity and onset of symptoms.
The analytical sensitivity of this test is expected to be high since this Next-Generation sequencing test is designed to detect nearly all clinically relevant sequence and copy number variants in genes that cause monogenic obesity.
Additional Sanger sequencing is performed for any regions not captured or with insufficient number of sequence reads.
This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.
Indications for Test
Candidates for this test are patients with non-syndromic obesity.
Candidates for this test are patients with non-syndromic obesity.
|Official Gene Symbol||OMIM ID|
- Albuquerque et al. 2015. PubMed ID: 25749980
- Farooqi and O'Rahilly. 2005. PubMed ID: 15660521
- Farooqi et al. 2003. PubMed ID: 12646665
- Fontaine et al. 2003. PubMed ID: 12517229
- Gusev et al. 2014. PubMed ID: 25439723
- Lu et al. 2000. PubMed ID: 11030331
- Millet et al. 1997. PubMed ID: 9389729
- Pigeyre et al. 2016. PubMed ID: 27154742
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
myPrevent - Online Ordering
- The test can be added to your online orders in the Summary and Pricing section.
- Once the test has been added log in to myPrevent to fill out an online requisition form.
- A completed requisition form must accompany all specimens.
- Billing information along with specimen and shipping instructions are within the requisition form.
- All testing must be ordered by a qualified healthcare provider.