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 ( Identifier: NCT03374956); dietary supplements ( 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.

Table 1: Overview of the genes included in Obesity panel

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
ALMS1 606844 Alstrom syndrome AR 62
ARL6 608845 Bardet-Biedl syndrome type 1; Bardet-Biedl syndrome 3; Retinitis pigmentosa 55 AR, DiR 7
BBIP1 613605 Bardet-Biedl syndrome 18 AR 1
BBS1 209901 Bardet-Biedl syndrome type 1 AR, DiR 14
BBS10 610148 Bardet-Biedl syndrome type 10 AR 12
BBS12 610683 Bardet-Biedl syndrome type 12 AR 8
BBS2 606151 Bardet-Biedl syndrome type 2; retinitis pigmentosa type 74 AR 16
BBS4 600374 Bardet-Biedl syndrome 4 AR 12
BBS5 603650 Bardet-Biedl syndrome 5 AR 27
BBS7 607590 Bardet-Biedl syndrome type 7 AR 17
BBS9 607968 Bardet-Biedl syndrome type 9 AR 23
CCDC28B 610162 Bardet-Biedl syndrome type 1 AR, DiR 1
CEP290 610142 Joubert syndrome type 5; Senior-Loken syndrome type 6; Meckel syndrome type 4; Leber congenital amaurosis type 10; Bardet-Biedl syndrome type 14 AR 52
DYRK1B 604556 Abdominal obesity-metabolic syndrome 3 AD 0
GNAS 139320 Pseudohypoparathyroidism Ia; Osseous heteroplasia, progressive; McCune-Albright syndrome, somatic, mosaic; ACTH-independent macronodular adrenal hyperplasia; Pseudohypoparathyroidism Ib; Pseudohypoparathyroidism Ic; Pseudopseudohypoparathyroidism AD 17
IFT27 615870 Bardet-Biedl syndrome 19 AR 0
LEP 164160 Leptin deficiency AR 3
LEPR 601007 AR 0
LZTFL1 606568 Bardet-Biedl syndrome 17 AR 6
MAGEL2 605283 Schaaf-Yang syndrome AD 8
MC4R 155541 0
MKKS 604896 McKusick-Kaufman syndrome; Bardet-Biedl syndrome type 6 AR 6
MKS1 609883 Meckel syndrome type 1; Bardet-Biedl syndrome type 13; Joubert syndrome type 28 AR 8
NR0B2 604630 OBESITY AD, AR 0
NTRK2 600456 ? Obesity, hyperphagia, and developmental delay AD 0
PCSK1 162150 Obesity with impaired prohormone processing AR 0
PHF6 300414 Borjeson-Forssman-Lehmann syndrome XLR 3
POMC 176830 OBESITY; Proopiomelanocortin Deficiency AD, AR 3
PPARG 601487 noninsulin-dependent diabetes mellitus / Diabetes mellitus type II; OBESITY; Lipodystrophy, familial partial, type 3 AD, AR 0
SDCCAG8 613524 Senior-Loken syndrome 7; Bardet-Biedl syndrome 16 AR 12
SIM1 603128 2
TRIM32 602290 limb-girdle muscular dystrophy type 2H; Bardet-Biedl syndrome 11 AR 3
TTC8 608132 retinitis pigmentosa type 51; Bardet-Biedl syndrome type 8 AR 13
UCP3 602044 OBESITY AD, AR 1
VPS13B 607817 Cohen syndrome AR 26
WDPCP 613580 Bardet-Biedl syndrome 15 AR 7