On this page, you will find information about a genetic change that was identified in a UDN participant.  

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Date of Report

Nov 13, 2017

Full Name

GNAS complex locus

Chromosome 20 (20q13.32)


The GNAS gene codes for an alpha subunit of the guanine nucleotide-binding protein (G protein) (Genetics Home Reference).

Database Links

GeneCards: GC20P058839

Genetics Home Reference: GNAS gene

NCBI Gene: 2778

OMIM: 139320

UniProtKB/Swiss-Prot: Q5JWF2

Clinical Significance

A change in the GNAS gene was identified in a UDN participant. The participant, a 12-year-old male with overgrowth, developmental delay, and behavior problems was found to carry the following genetic change in the GNAS gene: c.1235C>T / p.P412L.

Inheritance Pattern Autosomal dominant/imprinting
Position Chr20: 57429742
Transcript NM_001077490
DNA Change c.1235C>T
Protein Change p.P412L

After birth, the patient was found to be in respiratory distress. He had low levels of red blood cells (anemia), yellowing of the skin (jaundice caused by hyperbilirubinemia), and heartburn (gastroesophageal reflux). This required hospitalization in the NICU for 72 days.

Over time, the patient was noticed to have delayed milestones (global developmental delay), walking and talking at approximately 2 years of age. He progressed quickly afterward. However, he still has difficulty walking and currently uses a walker and sometimes a wheelchair. He experiences painful bone cracking and hand, foot, and ankle discomfort when walking.

At the age of 9, he was seen by endocrinology due to increased height and weight despite diet and exercise. Currently, he continues to grow at a fast pace with his clothing and shoe size going up over the span of just a few months.

Some of his other features include:

  • Accelerated skeletal maturation
  • Overgrowth
  • Large head size (macrocephaly)
  • Increased levels of insulin in blood (hyperinsulinemia)
  • Insulin resistance
  • Increased appetite (polyphagia)
  • Dark patches of thick, velvety skin (acanthosis nigricans)
  • Attention deficit hyperactivity disorder
  • Increased thickness of the heart (hypertrophic cardiomyopathy)
  • Heart defect (pulmonic stenosis)
  • Slow heart rate (bradycardia)
  • Sleep apnea (obstructive)
  • Asthma
  • Skin tags
  • Almond-shaped opening between the eyelids (palpebral fissure)
  • Heartburn (gastroesophageal reflux)
  • Increased volume of urine (polyuria)
  • Increased levels of cortisol in urine (increased urinary cortisol level)
  • Flat feet (pes planus)
  • Increased hormone secreted by the pituitary gland (increased circulating ACTH level)
  • Increased liver enzymes (elevated alkaline phosphatase)
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