ESRRB

ESRRB (Estrogen-Related Receptor Beta) is a nuclear receptor gene located on chromosome 14q24.3 that plays a crucial role in inner ear development, enamel formation, and cellular energy regulation. 

Although structurally similar to estrogen receptors, ESRRB functions independently to regulate transcription, influencing pluripotency, metabolic pathways, and ion transport, with mutations linked to hearing impairment, dental caries susceptibility, and metabolic disorders.

What is ESRRB (Estrogen-Related Receptor Beta)?

The ESRRB (Estrogen-Related Receptor Beta) gene, located on chromosome 14q24.3, encodes a nuclear receptor protein essential for inner ear development, enamel formation, and cellular energy regulation. 

While structurally similar to estrogen receptors, ESRRB functions independently in transcriptional regulation, influencing pluripotency, metabolic pathways, and ion transport.

Genetic Mutations and Disease Associations

The following conditions are associated with mutations in the ESRRB gene:

Hearing Impairment (DFNB35)

Biallelic ESRRB mutations disrupt cochlear function, leading to autosomal recessive nonsyndromic hearing loss (DFNB35).

These mutations affect sensory hair cell survival and ion homeostasis, resulting in progressive or congenital deafness.

Dental Caries Susceptibility

ESRRB is expressed during enamel development, influencing enamel hardness and resistance to decay.

Individuals with ESRRB mutations show higher dental caries rates, likely due to weaker enamel composition.

Pluripotency and Metabolic Regulation

ESRRB plays a role in stem cell maintenance and cellular energy homeostasis by regulating mitochondrial function and oxidative phosphorylation.

Clinical Implications

Genetic testing for ESRRB mutations may aid in the early diagnosis of hearing loss and enamel defects. Understanding ESRRB’s function provides potential therapeutic targets for hereditary deafness and dental health strategies.

Who Should Get ESRRB Tested?

The ESRRB (Estrogen-Related Receptor Beta) gene plays a crucial role in hearing, metabolism, and cellular energy production. Testing for ESRRB mutations can help identify genetic conditions linked to hearing loss, metabolic disorders, and autoimmune diseases. Here’s when clinicians should consider ordering ESRRB testing.

Patients with Genetic Hearing Loss Risks

Individuals with a family history of progressive hearing loss or congenital deafness may benefit from ESRRB testing. 

Mutations in ESRRB have been associated with nonsyndromic deafness (DFNB35), which can lead to sensorineural hearing impairment. Early identification allows for better hearing preservation strategies and early interventions.

Metabolic and Mitochondrial Disorder Cases

Patients presenting with chronic fatigue, muscle weakness, or unexplained metabolic dysfunction may have ESRRB-related metabolic abnormalities. 

ESRRB is involved in mitochondrial function, and mutations can impact energy metabolism, oxidative stress regulation, and overall cellular health.

Stem Cell Research and Therapy Candidates

ESRRB is essential in pluripotency and differentiation pathways, making it an important biomarker in stem cell research and regenerative medicine. 

Patients undergoing stem cell-based therapies or clinical trials may require ESRRB testing to evaluate cell fate decisions and optimize therapeutic outcomes.

Test Procedure and Interpretation

The following section outlines the testing procedures and interpretation.

Testing Procedure and Preparation

Genetic testing involves blood, saliva, or cheek swab samples, although specialized laboratories may recommend different sample types. 

A cheek swab or saliva sample is easily obtained from the comfort of home, while blood samples typically require a blood draw.

Normal Reference Ranges

Normal reference ranges for ESRRB genetic testing are considered to be without mutations that can alter the activity of the ESRRB proteins.

Clinical Implications of Positive ESRRB Mutations

The clinical implications of a positive ESRRB mutation test result will vary by individual, although ESRRB mutations in symptomatic patients may signal a need for further assessment and possibly treatment, especially in the setting of symptoms of hearing loss, unusual patterns of tooth decay, and/or metabolic disorders.

Patients or practitioners with questions about the clinical implications of ESRRB mutations should seek further assessment with a genetic counselor or expert. 

Clinical Implications of Negative ESRRB Mutations

A negative result does not rule out other genetic causes of hearing losses; additional genetic testing may be appropriate.