Test code: 3116

Congenital Obesity: Sequencing Panel
Test Code: 3116
Turnaround time: 6 weeks

CONDITION DESCRIPTION
Obesity is the thought to be the result of a combination of genetic and environmental factors (1). Polymorphisms in various genes controlling appetite and metabolism predispose to obesity under certain dietary conditions. The percentage of obesity that can be attributed to genetics varies widely, depending on the population examined, from 6% to 85% (2). As of 2006, more than 40 sites on the human genome have been linked to the development of obesity when a favorable environment is present (3). Some obesogenic or leptogenic genes may influence obese individuals’ response to weight loss or weight management (4). Obesity occurs when abnormal amounts of triglycerides are stored in adipose tissue and released as free fatty acids with detrimental effects. Obesity is linked to an increased risk of type 2 diabetes, cardiovascular disease, cancer, and mortality, and may be diagnosed as an isolated clinical finding or as part of multi-syndromic findings.

References:
1. Albuquerque D, Stice E et al. Current review of genetics of human obesity: from molecular mechanisms to an evolutionary perspective. Mol. Genet. Genomics. March 2015.
2. Yang W, Kelly T, He J. Genetic epidemiology of obesity. Epidemiol Rev. 2007. 29: 49–61.
3. Poirier P, Giles TD, Bray GA et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss. Arterioscler. Thromb. Vasc. Biol. May 2006. 26 (5): 968–76.
4. Hainer, Vojt??ch; Hermann Toplak; Asimina Mitrakou. Treatment Modalities of Obesity: What fits whom? Diabetes Care. February 2008. 31: 269–277.

GENES
ALMS1,  ARL6,  BBS1,  BBS10,  BBS12,  BBS2,  BBS4,  BBS5,  BBS7,  BBS9,  CEP290,  GNAS,  LEP,  LEPR, MAGEL2,  MC4R,  MKKS,  MKS1, NR0B2,  NTRK2,  PCSK1,  PHF6,  POMC,  SDCCAG8,  SIM1,  TRIM32,  TTC8,  VPS13B,  WDPCP

INDICATIONS
The test is indicated for:
• Individuals with a clinical or suspected diagnosis of congenital obesity.

METHODOLOGY
Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient’s genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not mean to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient’s gene sequences are then compared to a standard reference sequence.

DETECTION
Next Generation Sequencing: Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions/duplications will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient’s clinical/biochemical phenotype.

Analytical Sensitivity: ~99%.

SPECIMEN REQUIREMENTS

Submit only 1 of the following specimen types

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml.

Specimen Collection and Shipping: Ship sample at room temperature with overnight delivery.

Type: Isolated DNA
Specimen Requirements:
In microtainer: 30 ug
Isolation using the QiagenTM Puregene kit for DNA extraction is recommended.

Specimen Collection and Shipping: Refrigerate until time of shipment in 100 ng/ul of TE buffer. Ship sample at room temperature with overnight delivery.