Back
Publications about genetic testing for metabolic disorders
  1. Obesity Gene Panel

Obesity Gene Panel

July 27, 2018

Disease summary:

Obesity is an increasingly common complex condition caused by several genetic and non-genetic risk factors and it is correlated with increased risks for diabetes type 2, heart diseases and cancers 1. It is a neuroendocrine condition caused by combined effects of both environmental and genetic risk factors and/or predispositions 5, 6, 7.

The genetic causes of obesity can be classified as monogenic and syndromic forms8. Syndromic forms of obesity are caused by the genes: ALMS1, ARL6, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, CEP290, CUL4B, DYRK1B, GNAS, IFT27, LEP, LEPR, LZTFL1, MAGEL2, MC4R, MKKS, MKS1, NR0B2, NTRK2, PCSK1, PHF6, POMC, SDCCAG8, SIM1, TRIM32, TTC8, UCP3, VPS13B, WDPCP (Table 1). Monogenic forms of obesity are associated with pathogenic variants in the MC4R, LEP, LEPR, PCSK1 and POMC genes (Table 2). 


Autosomal dominant, autosomal recessive, digenic recessive, X-linked

Increasing prevalence for non-genetic forms of obesity

Major clinical symptoms 1:

  • Severe early-onset obesity and hyperphagia
  • Increased linear growth and delayed puberty
  • Psychological changes (depression, anxiety and other)
  • Hyperinsulinemia and/or hypocortisolemia                                                          

Overview of symptoms in specific syndromic forms of obesity is given in Table 1.

  • Presence of abnormal obesity from the earliest ages
  • Laboratory analyses of serum and urine showing abnormal levels of glucose, lipids, and other substances
  • Positive family history of disease
  • Identification of a pathogenic variant in one of the associated genes for syndromic (Table 1) and monogenic forms of obesity (Table 2).

Depending on the genetic background of obesity, the treatment is based on changes in the lifestyle or additional managements, including the following:

  • Diet, exercise and behavioral modification
  • Pharmacotherapy, monitoring of blood sugar levels, blood pressure and other complications
  • Ongoing clinical trials are in progress, testing new potential drugs for obesity, including: Phentermine-Topiramate; Liraglutide; Naltrexone/bupropion; Phentermine (ClinicalTrials.gov Identifier: NCT03374956); dietary supplements (ClinicalTrials.gov Identifier: NCT02733484) and others.
  • Type 2 diabetes mellitus
  • Cushing syndrome
  • Hypothyroidism
  • Insulinoma
  • Kallmann syndrome and idiopathic hypogonadotropic hypogonadism
  • Generalized lipodystrophy

To confirm/establish the diagnosis, CENTOGENE offers the following tests:

  • Obesity NGS Panel which includes sequencing of the genes ALMS1, ARL6, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, CEP290, CUL4B, DYRK1B, GNAS, IFT27, LEP, LEPR, LZTFL1, MAGEL2, MC4R, MKKS, MKS1, NR0B2, NTRK2, PCSK1, PHF6, POMC, SDCCAG8, SIM1, TRIM32, TTC8, UCP3, VPS13B, WDPCP
  • Obesity NGS Panel + CNV which includes sequencing and additionally detection of large deletions and duplications from the NGS data for the above genes
  • Individuals with a positive family history of obesity
  • Individuals with most common symptoms of obesity (regardless of family history)

Confirmation of a clinical diagnosis through genetic testing of obesity can allow for genetic counseling and may direct medical management.