DFNB49 nonsyndromic deafness

Overview

DFNB49 non-syndromic deafness also known as dfnb 49 nonsyndromic hearing loss and deafness, is an inherited condition caused by mutations in the gene TRIC. Its "non-syndromic" designation means the hearing loss has not previously been linked to any other medical conditions.

Symptoms

Nonsyndromic deafness is hearing loss that is not associated with other signs and symptoms. In contrast, syndromic deafness involves hearing loss that occurs with abnormalities in other parts of the body.

Most forms of nonsyndromic deafness are associated with permanent hearing loss caused by damage to structures in the inner ear. The inner ear consists of three parts: a snail-shaped structure called the cochleathat helps process sound, nerves that send information from the cochlea to the brain, and structures involved with balance. Loss of hearing caused by changes in the inner ear is called sensorineural deafness. Hearing loss that results from changes in the middle ear is called conductive hearing loss. The middle ear contains three tiny bones that help transfer sound from the eardrum to the inner ear. Some forms of nonsyndromic deafness involve changes in both the inner ear and the middle ear; this combination is called mixed hearing loss.

The severity of hearing loss varies and can change over time. It can affect one ear (unilateral) or both ears (bilateral). Degrees of hearing loss range from mild (difficulty understanding soft speech) to profound (inability to hear even very loud noises). The loss may be stable, or it may progress as a person gets older. Particular types of nonsyndromic deafness often show distinctive patterns of hearing loss. For example, the loss may be more pronounced at high, middle, or low tones.

Nonsyndromic deafness can occur at any age. Hearing loss that is present before a child learns to speak is classified as prelingual or congenital. Hearing loss that occurs after the development of speech is classified as postlingual.

Causes

Genetic changes are related to the following types of nonsyndromic deafness.

• DFNA: nonsyndromic deafness, autosomal dominant
• DFNB: nonsyndromic deafness, autosomal recessive
• DFNX: nonsyndromic deafness, X-linked
• nonsyndromic deafness, mitochondrial

DFNB49 is caused by mutation in the gene encoding tricellulin (MARVELD2). All of these mutations resulted in proteins that lacked the ability to bind to the scaffolding protein ZO1 (601009) because of the loss of the conserved C-terminal occludin-ELL domain. Loss of tricellulin disrupted the structure of what are called tight junctions in the epithelial cells of the cochlea in the inner ear. This affected the permeability of inner ear epithelia tissue, creating a possible channel that caused an imbalance in the quantity of ions and macromolecules. It resulted in a detrimental environment and loss of cochlear hair cells, leading to hearing loss.

Source:

J Clin Invest. 123(9), 4036–4049.

Prevention

The inner ear has fluid-filled compartments of different ionic compositions, including the endolymphatic and perilymphatic spaces of the organ of Corti; the separation from one another by epithelial barriers is required for normal hearing. TRIC encodes tricellulin, a recently discovered tight-junction (TJ) protein that contributes to the structure and function of tricellular contacts of neighboring cells in many epithelial tissues.

Source:

Am J Hum Genet. 2006 Dec;79(6):1040-51.

Diagnosis

Genome screening using either ~400 microsatellite or ~6,000 single nucleotide polymorphism (SNP) marker loci.

Source:

J Hum Genet. 2008;53(2):101-5.