Autoimmune disease in a DFNA6/14/38 family carrying a novel missense mutation in WFS1.

Most familial cases of autosomal dominant low frequency sensorineural hearing loss (LFSNHL) are attributable to mutations in the wolframin syndrome 1 (WFS1) gene at the DFNA6/14/38 locus. WFS1 mutations at this locus were first described in 2001 in six families segregating LFSNHL that was non-progressive below 2,000 Hz; the causative mutations all clustered in the C-terminal domain of the wolframin protein. Mutations in WFS1 also cause Wolfram syndrome (WS), an autosomal recessive neurodegenerative disorder defined by diabetes mellitus, optic atrophy and often deafness, while numerous single nucleotide polymorphisms (SNPs) in WFS1 have been associated with increased risk for diabetes mellitus, psychiatric illnesses and Parkinson disease.

SIX1 mutation screening in 247 branchio-oto-renal syndrome families: a recurrent missense mutation associated with BOR.

Branchio-oto-renal syndrome (BOR) is a clinically heterogeneous autosomal dominant form of syndromic hearing loss characterized by variable hearing impairment, malformations of the pinnae, the presence of branchial arch remnants, and various renal abnormalities. Both EYA1 and SIX1 are expressed in developing otic, branchial and renal tissue. Consistent with this expression pattern, mutations in both genes cause BOR syndrome.

Branchio-oto-renal syndrome (BOR): novel mutations in the EYA1 gene, and a review of the mutational genetics of BOR.

Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder characterized by the association of branchial and external ear malformations, hearing loss, and renal anomalies. The phenotype varies from ear pits to profound hearing loss, branchial fistulae, and kidney agenesis. The most common gene mutated in BOR families is EYA1, a transcriptional activator.

Genotype-phenotype correlations for SLC26A4-related deafness.

Pendred syndrome (PS) and non-syndromic enlarged vestibular aqueduct (EVA) are two recessive disorders characterized by the association of sensorineural hearing loss (SNHL) with inner ear malformations that range from isolated EVA to Mondini Dysplasia, a complex malformation that includes a cochlear dysplasia and EVA. Mutations in the SLC26A4 gene, coding for the protein pendrin, have been implicated in the pathophysiology of both disorders. In order to determine whether SLC26A4 genotypes can be correlated to the complexity and severity of the phenotypes, we ascertained 1,506 deaf patients.