GNAS mutations can cause obesity in children due to their affect on MC4r

Before I write most blog posts, I research like a crazy person. My blog is all about MC4r and sometimes other weight-related genetic disorders. It’s about awareness, it’s about breaking down the stigma around obesity, and essentially you can’t judge a book by its cover, and that a persons lifestyle doesn’t always reflect their body type.

What I have found recently is that many newspapers have gripped onto this concept. They’ve spoken to the “experts” and it’s why we’re now hearing about genetic causes of obesity in mainstream media.

While I’m glad that it’s hit the mainstream and more people are aware of genetic causes and their link to obesity; I dislike the way it’s being reported. Personally I feel the articles are not educational and provide little to no information about identifying genetic disorders, or getting them diagnosed — which is frustrating considering they’re talking to “experts” the field of medicine.

So in the spirt of education, I’m going to share a recent study conducted in December 2021 that could detect genetic disorders in children with severe childhood-onset obesity.

The study concluded that GNAS mutations can cause obesity in children due to their affect on melanocortin 4 receptor (MC4R) signalling.

SIDE NOTE: GNAS complex locus is a gene locus in humans. Its main product is the heterotrimeric G-protein alpha subunit Gs-α, a key component of G protein-coupled receptor-regulated adenylyl cyclase signal transduction pathways. GNAS stands for Guanine Nucleotide binding protein, Alpha Stimulating activity polypeptide.

Investigators conducted exome sequencing and targeted resequencing in 2548 children with severe obesity and unexpectedly found GNAS mutations in 22 of the participants.

Here are some of the key findings:

  • In the first 6 months of life, all patients had accelerated weight gain that led to severe obesity in childhood.
  • The study authors identified 19 heterozygous GNASmutations in 22 children with severe childhood-onset obesity, including 16 missense, 2 nonsense, and 1 frameshift mutation.
  • Children who had GNAS mutations had accelerated growth before age 12.
  • In 14 of 18 children with GNASmutations, growth trajectories before age 12 years were comparable with those in other severely obese children.
  • Six of 11 GNAS mutation carriers had a reduction in pubertal growth spurt, final height, or both.
  • Participants who had a reduction in pubertal growth spurt carried GNAS mutations that impaired growth hormone–releasing and hormone receptor signalling.

Due to the fact that the mutation manifests with obesity alone, screening for GNAS deficiency could allow for early diagnosis for genetic disorders and improve clinical outcomes for MC4r agonists aiding in weight loss and/or maintenance.

The scientific and medical world is forever expanding and as it does, we learn more about genetic obesity disorders. This is a platform I hope you can use to understand them and together, let’s break down obesity stigma because whether it’s a gene or a lifestyle habit at the end of the day, we’re only human, and life is too short.

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