autosomal recessive nonsyndromic deafness 114

Autosomal Recessive Nonsyndromic Deafness 114, also known as DFNB114, is a rare genetic disorder characterized by congenital profound sensorineural hearing loss.

• Definition: It is an autosomal recessive nonsyndromic deafness characterized by congenital profound sensorineural hearing loss that has material basis in homozygous or compound heterozygous mutation in the GRAP gene on chromosome 17p11.2 [3][5].
• Prevalence: The prevalence of this condition is unknown.
• Inheritance: It follows an autosomal recessive inheritance pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to express the condition.
• Age of onset: Symptoms are typically present at birth.

This condition is one of many forms of autosomal recessive nonsyndromic hearing loss, which accounts for more than 50% of cases in some populations [2]. The GRAP gene plays a crucial role in this disorder, and mutations in this gene have been identified as the cause of DFNB114.

Autosomal recessive nonsyndromic deafness 114, also known as DFNB114, is a genetic disorder that affects hearing. The clinical features of this condition are well-documented in medical literature.

Prelingual Onset: Individuals with autosomal recessive nonsyndromic deafness 114 typically experience profound sensorineural hearing loss from birth or early childhood [1]. This means that they have significant difficulty hearing sounds, especially at higher frequencies.

Stable Hearing Loss: The hearing loss associated with DFNB114 is generally stable and non-progressive, meaning it does not worsen over time [8].

Profound Deafness: All affected individuals have profound deafness, which implies a severe to profound loss of hearing in both ears [5].

Vestibular Dysfunction: Some people with autosomal recessive nonsyndromic deafness 114 may also experience vestibular dysfunction, which affects balance and equilibrium [5].

Retinitis Pigmentosa: In almost all affected individuals, retinitis pigmentosa (a condition that causes progressive vision loss) begins to manifest [5].

It's essential to note that the signs and symptoms of autosomal recessive nonsyndromic deafness 114 can vary in severity and impact on daily life. However, the primary characteristic is profound sensorineural hearing loss from birth or early childhood.

References: [1] Li et al., 2019 - Characterized by congenital profound sensorineural hearing loss. [5] Bork JM, 2001 - All affected individuals have profound deafness, evidence of vestibular dysfunction, and retinitis pigmentosa that, in almost all affected individuals, began ... [8] Vona B, 2015 - For example, autosomal recessive NSHL is generally prelingual, non-progressive (stable) and severe-to-profound [2].

Autosomal recessive nonsyndromic deafness (ARNSD) is a genetic disorder that affects hearing, and diagnostic tests play a crucial role in identifying the condition. Here are some key points about diagnostic tests for ARNSD:

• Genetic testing: Molecular genetic testing is available for many types of syndromic and nonsyndromic deafness, including ARNSD [9]. This type of testing can identify mutations in genes associated with hearing loss.
• GJB2-related ARNSD: The diagnosis of GJB2-related autosomal recessive nonsyndromic hearing loss (GJB2-AR NSHL) is established in a proband with suggestive findings and confirmed by genetic testing [10].
• STRC-HL: Diagnostic tests for STRC-related autosomal recessive hearing loss (STRC-HL) include genetic testing to identify mutations in the STRC gene.
• Common genes associated with hearing loss: Genes such as GJB2, GJB6, SLC26A4, and OTOF are common causes of hearing loss and can be tested for using diagnostic tests [13].
• Diagnostic yield: The diagnostic yield of different genetic tests for nonsyndromic hearing loss (NSHL) varies, but some studies have reported a high diagnostic yield for certain genes [8].

In terms of specific diagnostic tests, the following may be used:

• Genetic panel testing: This type of testing involves analyzing multiple genes associated with hearing loss simultaneously.
• Next-generation sequencing (NGS): NGS is a powerful tool for identifying genetic mutations and can be used to diagnose ARNSD.
• Sanger sequencing: This type of sequencing is often used to confirm the presence of specific mutations identified by other tests.

It's essential to note that diagnostic testing for ARNSD should only be performed under the guidance of a qualified healthcare professional. If you suspect you or someone in your family may have ARNSD, consult with a genetic counselor or a healthcare provider who specializes in genetics and hearing loss.

References:

[8]

Current Therapies for Autosomal Recessive Nonsyndromic Deafness

Unfortunately, there are no biological therapies currently available to treat autosomal recessive nonsyndromic deafness. The current treatment options for this condition are limited to:

• Hearing Aids: These devices can amplify sound and improve communication, but they do not restore hearing.
• Cochlear Implants: These medical devices can bypass damaged or non-functioning parts of the ear and directly stimulate the auditory nerve, allowing some individuals with severe to profound sensorineural hearing loss to perceive sound.

Experimental Treatments

However, there are ongoing research efforts exploring new therapeutic approaches for autosomal recessive nonsyndromic deafness. Some experimental studies have demonstrated improvements in hearing following a single local injection of adeno-associated virus-derived vectors carrying an additional normal gene or using ribozymes to modify the genome [10][12].

Additionally, gene therapy has shown promise as a potential treatment for this condition. A recent study published in Molecular Therapy Nucleic Acids demonstrated the efficacy of a tissue-specific gene therapy in a model of autosomal recessive hearing loss 9 (DFNB89), caused by a pathogenic mutation of the OTOF gene [13]. Gene therapy may offer curative effects and clinical benefit for individuals with this condition.

Future Directions

Gene therapy promises to be a clinically useful method to cure deafness, in particular genetic deafness [14]. Researchers are actively exploring the mechanisms underlying genetic deafness and possible treatment measures using gene therapy. A recent study reported the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene as a treatment for children with autosomal recessive deafness 9 [15].

References:

[10] Experimental studies have demonstrated improvements in hearing following a single local injection of adeno-associated virus-derived vectors carrying an additional normal gene or using ribozymes to modify the genome. [12] Experimental studies have demonstrated improvements in hearing following a single local injection of adeno-associated virus-derived vectors carrying an additional normal gene or using ribozymes to modify the genome. [13] A recent study published in Molecular Therapy Nucleic Acids has demonstrated the efficacy of a tissue-specific gene therapy in a model of autosomal recessive hearing loss 9 (DFNB89), caused by a pathogenic mutation of the OTOF gene. [14] Gene therapy promises to be a clinically useful method to cure deafness, in particular genetic deafness. [15] In this Article, we report the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9.

Here are some potential differential diagnoses for autosomal recessive nonsyndromic deafness:

1. Congenital cytomegalovirus (CMV) infection: CMV is a common viral infection that can cause hearing loss, among other symptoms.
2. Toxoplasmosis: This parasitic infection can also cause congenital hearing loss.
3. Rubella: Congenital rubella syndrome can lead to hearing loss, among other complications.
4. Syphilis: Congenital syphilis can cause a range of symptoms, including hearing loss.
5. Hemophilus influenzae type b (Hib) infection: This bacterial infection can cause meningitis and hearing loss in infants.
6. Meningitis: Bacterial or viral meningitis can cause hearing loss due to inflammation of the inner ear.
7. Otosclerosis: A condition where abnormal bone growth in the middle ear causes hearing loss.
8. Meniere's disease: A disorder of the inner ear that can cause vertigo, tinnitus, and hearing loss.
9. Acoustic neuroma: A non-cancerous tumor on the nerve connecting the inner ear to the brain, which can cause hearing loss.
10. Genetic syndromes: Certain genetic syndromes, such as Down syndrome or Turner syndrome, can increase the risk of hearing loss.

It's essential to note that autosomal recessive nonsyndromic deafness is a specific diagnosis, and these differential diagnoses should be considered in cases where the diagnosis is unclear or when there are additional symptoms present.

In terms of clinical presentation, patients with autosomal recessive nonsyndromic deafness typically have:

• Bilateral sensorineural hearing loss
• Onset at birth or early childhood
• No other associated medical conditions or physical abnormalities
• Family history of similar hearing loss

A thorough medical and family history, along with audiologic evaluation and genetic testing (if necessary), can help confirm the diagnosis of autosomal recessive nonsyndromic deafness.