Monogenic and Syndromic Obesity
The heritability of obesity is estimated between 40-70%, but the genetics of obesity for most individuals is complex and involves the interaction of multiple genes with the environment.
Overview
The heritability of obesity is estimated between 40-70%, but the genetics of obesity for most individuals is complex and involves the interaction of multiple genes with the environment. There are however several syndromic and non-syndromic forms of obesity that are monogenic and oligogenic that provide insight into the underlying molecular control of food intake and the mechanisms that control ingestive behavior and satiety to regulate body weight. The mode of inheritance is typically autosomal dominant.
The Igenomix Monogenic and Syndromic Precision Panel can be used to make a directed and accurate differential diagnosis of obesity, ultimately leading to a better management and prognosis of the disease and its outcomes. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
Indication
The Igenomix Monogenic and Syndromic Obesity Precision Panel is indicated for those patients with obesity with or without family history of obesity presenting with the following manifestations:
- Abnormal weight growth pattern
- Elevated body mass index
- Hypertension
- Type 2 diabetes
- Metabolic Syndrome
Clinical Utility
The clinical utility of this panel is:
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- Early initiation of treatment with a multidisciplinary team for early pharmacologic therapy, surgical intervention, and/or dietary modifications to reduce comorbidities associated with obesity.
- Risk assessment of asymptomatic family members according to the mode of inheritance.
Genes & Diseases
See all genes & diseases
| GENE | OMIM DISEASES | INHERITANCE* | % GENE COVERAGE (20X) | HGMD** |
| ADCY3 | Body Mass Index Quantitative Trait Locus | AR | 97.98% | 7 of 7 |
| AFF4 | Chops Syndrome, Cognitive Impairment-Coarse Facies-Heart Defects-Obesity-Pulmonary Involvement-Short Stature-Skeletal Dysplasia Syndrome | AD | 99.42% | 6 of 6 |
| ALMS1 | Alstrom Syndrome | AR | 99.92% | 302 of 305 |
| ARL6 | Bardet-Biedl Syndrome, Retinitis Pigmentosa | AD,AR,X,XR,G | 100% | 17 of 21 |
| BBIP1 | Bardet-Biedl Syndrome | AR | 99.88% | 1 of 1 |
| BBS1 | Bardet-Biedl Syndrome | AR | 100% | 102 of 105 |
| BBS10 | Bardet-Biedl Syndrome | AR | 100% | 114 of 114 |
| BBS12 | Bardet-Biedl Syndrome | AR | 99.78% | 61 of 61 |
| BBS2 | Bardet-Biedl Syndrome, Retinitis Pigmentosa | AR | 100% | 99 of 100 |
| BBS4 | Bardet-Biedl Syndrome | AR | 100% | 45 of 48 |
| BBS5 | Bardet-Biedl Syndrome | AR | 99.80% | 30 of 31 |
| BBS7 | Bardet-Biedl Syndrome | AR | 100% | 48 of 48 |
| BBS9 | Bardet-Biedl Syndrome | AR | 99.56% | 50 of 51 |
| C8ORF37 | Bardet-Biedl Syndrome, Cone Rod Dystrophy, Retinitis Pigmentosa | AD,AR,X,XR,G | na | na |
| CEP19 | Morbid Obesity And Spermatogenic Failure | AR | 99.88% | 2 of 2 |
| CEP290 | Bardet-Biedl Syndrome, Joubert Syndrome, Joubert Syndrome With Oculorenal Defect, Leber Congenital Amaurosis, Meckel Syndrome, Senior-Loken Syndrome | AR | 96.47% | 293 of 327 |
| CUL4B | X-Linked Mental Retardation With Short Stature, Small Testes, Musclewasting, And Tremor, X-linked Intellectual Disability, Cabezas Type | X,XR,G | 99.77% | NA of NA |
| DYRK1B | Abdominal Obesity-Metabolic Syndrome | AD | 99.72% | 3 of 3 |
| GNAS | ACTH-Independent Macronodular Adrenal Hyperplasia, Albright Hereditary Osteodystrophy, Cushing Syndrome, Mazabraud Syndrome, McCune-Albright Syndrome, Progressive Osseous Heteroplasia, Pseudohypoparathyroidism Type 1A Pseudohypoparathyroidism Type 1B, Pseudohypoparathyroidism Type 1C, Pseudopseudohypoparathyroidism | AD | 99.95% | 263 of 273 |
| IFT172 | Bardet-Biedl Syndrome, Jeune Syndrome, Retinitis Pigmentosa, Short-Rib Thoracic Dysplasia | AR | 100% | 37 of 37 |
| IFT27 | Bardet-Biedl Syndrome | AR | 100% | 5 of 5 |
| IFT74 | Bardet-Biedl Syndrome | AR | 99.95% | 6 of 6 |
| KIDINS220 | Spastic Paraplegia-Intellectual Disability-Nystagmus-Obesity Syndrome | AD | 99.83% | 17 of 17 |
| KSR2 | Obesity, Insulin Resistance and Impaired Cellular Fuel Oxidation | 99.88% | 29 of 29 | |
| LEP | Leptin Deficiency Or Dysfunction | AR | 100% | 19 of 19 |
| LEPR | Leptin Receptor Deficiency | AR | 97.92% | 49 of 49 |
| LZTFL1 | Bardet-Biedl Syndrome | AR | 99.83% | 4 of 4 |
| MAGEL2 | MAGEL2-related Prader-Willi-Like Syndrome, Prader-Willi Syndrome | AD | 99.99% | 43 of 48 |
| MC4R | Body Mass Index Quantitative Trait Locus, Obesity Due To Melanocortin 4 Receptor Deficiency | AD,AR | 100% | 165 of 166 |
| MKKS | Bardet-Biedl Syndrome, Mckusick-Kaufman Syndrome | AR | 89.96% | 71 of 71 |
| MKS1 | Bardet-Biedl Syndrome, Joubert Syndrome, Joubert Syndrome With Ocular Defect, Meckel Syndrome | AR | 99.98% | 49 of 49 |
| MYT1L | Autosomal Dominant Mental Retardation, MRD39 chromosome 2p25.3 Deletion Syndrome | AD | 99.98% | 30 of 30 |
| NR0B2 | Obesity | AD,AR,MU,P | 99.09% | 15 of 15 |
| NTRK2 | Early Infantile Epileptic Encephalopathy, Obesity, Hyperphagia, And Developmental Delay, Undetermined Early-onset Epileptic Encephalopathy, West Syndrome | AD | 100% | 9 of 9 |
| PCSK1 | Obesity Due To Prohormone Convertase I Deficiency, Proprotein Convertase 1 Deficiency | AR | 99.98% | 45 of 45 |
| PHF6 | Borjeson-Forssman-Lehmann Syndrome | X,XR,G | 99.93% | NA of NA |
| PHIP | Developmental Delay, Intellectual Disability, Obesity, And Dysmorphic Features | AD | 98.74% | 51 of 52 |
| POMC | Obesity Due To Pro-Opiomelanocortin Deficiency | AD,AR,MU,P | 99.98% | 40 of 40 |
| PPARG | Berardinelli-Seip Congenital Lipodystrophy, Carotid Intimal Medial Thickness, Noninsulin-Dependent Diabetes Mellitus, Familial Partial Lipodystrophy, Obesity, PPARG-related Familial Partial Lipodystrophy | AD,AR,MU,P | 99.94% | 53 of 53 |
| PRMT7 | Short Stature-Brachydactyly-Obesity-Global Developmental Delay Syndrome | AR | 100% | 13 of 14 |
| RAI1 | 17p11.2 Microduplication Syndrome, PMP22-RAI1 Contiguous Gene Duplication Syndrome, Smith-Magenis Syndrome | AD | 99.91% | 50 of 53 |
| SDCCAG8 | Bardet-Biedl Syndrome, Senior-Loken Syndrome | AR | 96.29% | 18 of 19 |
| SETD2 | Luscan-Lumish Syndrome, Sotos Syndrome | AD | 99.83% | 19 of 19 |
| SH2B1 | Distal 16p11.2 Microdeletion Syndrome, Proximal 16p11.2 Microdeletion Syndrome, Severe Early-Onset Obesity-Insulin Resistance Syndrome Due To Sh2b1 Deficiency | 99.98% | 25 of 25 | |
| SIM1 | 6q16 Microdeletion Syndrome, Obesity Due To SIM1 Deficiency, SIM1-Related Prader-Willi-Like Syndrome | 99.64% | 39 of 40 | |
| TRIM32 | Bardet-Biedl Syndrome, Limb-Girdle Muscular Dystrophy Type 2H, TRIM32-Related Limb-Girdle Muscular Dystrophy | AR | 100% | 17 of 17 |
| TTC8 | Bardet-Biedl Syndrome, Retinitis Pigmentosa | AR | 99.33% | 28 of 28 |
| UCP3 | Obesity | AD,AR,MU,P | 99.98% | 6 of 6 |
| VPS13B | Cohen Syndrome | AR | 99.98% | 182 of 190 |
| WDPCP | Bardet-Biedl Syndrome, Congenital Heart Defects, Hamartomas Of Tongue, And Polysyndactyly, Meckel Syndrome | AR | 99.30% | 8 of 8 |
*Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial.
**Number of clinically relevant mutations according to HGMD
References
Rohde, K., Keller, M., la Cour Poulsen, L., Blüher, M., Kovacs, P., & Böttcher, Y. (2019). Genetics and epigenetics in obesity. Metabolism: clinical and experimental, 92, 37–50. https://doi.org/10.1016/j.metabol.2018.10.007
Reddon, H., Guéant, J. L., & Meyre, D. (2016). The importance of gene-environment interactions in human obesity. Clinical science (London, England : 1979), 130(18), 1571–1597. https://doi.org/10.1042/CS20160221
Kleinberger, J. W., Copeland, K. C., Gandica, R. G., Haymond, M. W., Levitsky, L. L., Linder, B., Shuldiner, A. R., Tollefsen, S., White, N. H., & Pollin, T. I. (2018). Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial. Genetics in medicine : official journal of the American College of Medical Genetics, 20(6), 583–590. https://doi.org/10.1038/gim.2017.15
