Schraders et al. (2012) studied 4 sibs with nonsyndromic deafness, who all had flat to shallow U-shaped audiograms. Of the 4 affected sibs, 3 had delayed speech development, suggesting a prelingual onset of the hearing impairment, and 2 ... Schraders et al. (2012) studied 4 sibs with nonsyndromic deafness, who all had flat to shallow U-shaped audiograms. Of the 4 affected sibs, 3 had delayed speech development, suggesting a prelingual onset of the hearing impairment, and 2 had delayed motor development, suggestive of vestibular problems at a young age. Rotary chair and caloric tests performed at the ages of 19 years, 17 years, 15 years, and 13 years in the 4 sibs, respectively, demonstrated vestibular hyporeflexia in all; CT scan in 1 sib revealed no inner ear abnormalities. Schraders et al. (2012) also studied 2 Spanish sibs with bilateral moderate sensorineural hearing impairment, in whom serial audiograms demonstrated nonprogression. The shape of their audiograms was slightly downsloping across all frequencies, and prelingual onset was suggested due to delayed speech development in both sibs. They had normal motor development and no dizziness or walking instability in adulthood. Oculomotor and rotatory chair testing by videonystagmography were normal in both sibs; however, bithermal caloric testing revealed a bilateral deficit consistent with subclinical vestibular dysfunction.
In 4 sibs from a Dutch family segregating autosomal recessive nonsyndromic deafness mapping to chromosome 11p15, Schraders et al. (2012) analyzed the USH1C gene (605242) but found no mutations. However, homozygosity for a 1-bp deletion in the candidate ... In 4 sibs from a Dutch family segregating autosomal recessive nonsyndromic deafness mapping to chromosome 11p15, Schraders et al. (2012) analyzed the USH1C gene (605242) but found no mutations. However, homozygosity for a 1-bp deletion in the candidate gene OTOG (5508delC; 604487.0001) was identified in the 4 affected sibs; the deletion was present in heterozygosity in their unaffected parents and was not found in controls. Sanger sequencing excluded mutations in 11 other genes within the region of shared homozygosity. Analysis of the OTOG gene in 60 Spanish families with autosomal recessive nonsyndromic deafness, in which mutation in the GJB2 (121011) and GJB6 (604418) genes had been excluded, revealed 2 sibs who were compound heterozygous for a missense (P2116L; 604487.0002) and a nonsense (R2187X; 604487.0003) mutation. Screening of 85 additional Dutch patients with autosomal recessive nonsyndromic deafness for the 5508delC deletion did not reveal any carriers, and no causative variants in the OTOG gene were found in 12 Dutch index patients with audiograms similar to those of patients with OTOG mutations or in 13 Turkish probands who were homozygous for markers flanking the OTOG gene.