KIT gene mutation causes deafness and hypopigmentation in Bama miniature pigs

Area of Science:

• Genetics
• Otolaryngology
• Developmental Biology

Background:

• Waardenburg syndrome (WS) is a common genetic disorder causing hearing loss and pigmentation abnormalities.
• Existing gene panels do not identify mutations in all WS patients, indicating undiscovered causative genes.

Purpose of the Study:

• To investigate the role of the KIT gene in Waardenburg syndrome.
• To identify novel genes associated with syndromic hearing loss.

Main Methods:

• Established an autosomal-dominant KIT mutation (c.2418T>A, p.Asp806Glu) pig model exhibiting WS-like phenotypes.
• Performed histological analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) on cochlear tissues.
• Measured endocochlear potentials to assess cochlear function.

Main Results:

• The KIT mutation caused congenital bilateral severe sensorineural hearing loss and hypopigmentation in pigs.
• Hair cell degeneration was observed starting at E100, with complete absence by P1.
• Stria vascularis (SV) showed disorganization and loss of intermediate cells, leading to dysfunction and absence of endocochlear potentials.

Conclusions:

• The KIT mutation (c.2418T>A, p.Asp806Glu) disrupts cochlear melanocyte development, causing SV malformation and dysfunction, ultimately leading to hair cell degeneration and hearing loss.
• KIT is identified as a potential novel gene associated with Waardenburg syndrome.
• Clinical screening for WS should consider including the KIT gene.