Broadening the Phenotype of DFNB28: Mutations in TRIOBP are associated with Moderate, Stable Hereditary Hearing Impairment.

Broadening the Phenotype of DFNB28: Mutations in TRIOBP are associated with Moderate, Stable Hereditary Hearing Impairment.
Hear Res. 2017 Jan 12;:
Authors: Wesdorp M, van de Kamp JM, Hensen EF, Schraders M, Oostrik J, Yntema HG, Feenstra I, Admiraal RJ, Kunst HP, Tekin M, Kanaan M, Kremer H, Pennings RJ
Abstract
DFNB28 is characterized by prelingual, severe to profound sensorineural hearing impairment (HI). It is associated with mutations in exon 6 and 7 of TRIOBP and has not been reported in the European population. Here, we describe two isolated cases of Dutch origin with congenital, moderate HI and compound heterozygous mutations in TRIOBP. Three of the mutations are novel, one nonsense mutation (c.5014G>T (p.Gly1672*)) and two frameshift mutations (c.2653del (p.Arg885Alafs*120) and c.3460_3461del (p.Leu1154Alafs*29)). The fourth mutation is the known c.3232dup (p.Arg1078Profs*6) mutation. Longitudinal audiometric analyses in one of the subjects revealed that HI was stable over a period of 15 years. Vestibular function was normal. Predicted effects of the mutations do not explain the relatively mild phenotype in the presented subjects, whereas location of the mutation might well contribute to the milder HI in one of the subjects. It is known that isoform classes TRIOBP-4 and TRIOBP-5 are important for stereocilia stability and rigidity. To our knowledge, p.Gly1672* is the first pathogenic variant identified in DFNB28 that does...

Source: Hearing Research - January 11, 2017 Category: Audiology Authors: Wesdorp M, van de Kamp JM, Hensen EF, Schraders M, Oostrik J, Yntema HG, Feenstra I, Admiraal RJ, Kunst HP, Tekin M, Kanaan M, Kremer H, Pennings RJ Tags: Hear Res Source Type: research