Cochlear Implantation in a Patient with a Novel POU3F4 Mutation and Incomplete Partition Type-III Malformation

Abstract

Aims. This study is aimed at (1) analyzing the clinical manifestations and genetic features of a novel POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family and (2) reporting the outcomes of cochlear implantation in a patient with this mutation. Methods. A patient who was diagnosed as the IP-III malformation underwent cochlear implantation in our hospital. The genetic analysis was conducted in his family, including the whole-exome sequencing combined with Sanger sequencing and bioinformatic analysis. Clinical features, preoperative auditory and speech performances, and postoperative outcomes of cochlear implant (CI) were assessed on the proband and his family. Results. A novel variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was detected in the family, which was cosegregated with the hearing loss. This variant was absent in 200 normal-hearing persons. The phylogenetic analysis and structure modeling of Pou3f4 protein further confirmed that the novel mutation was pathogenic. The proband underwent cochlear implantation on the right ear at four years old and gained greatly auditory and speech improvement. However, the benefits of the CI declined about three and a half years postoperation. Though the right ear had been reimplanted, the outcomes were still worse than before. Conclusion. A novel frame shift variant c.400_401insACTC (p.Q136LfsX58) in the POU3F4 gene was identified in a Chinese family with X-linked inheritance hearing loss. A patient with this mutation and IP-III malformation could get good benefits from CI. However, the outcomes of the cochlear implantation might decline as the patient grows old.

Genetic Load of Alternations of Transcription Factor Genes in Non-Syndromic Deafness and the Associated Clinical Phenotypes: Experience from Two Tertiary Referral Centers

“…Either intraoperative CSF gushers during electrode insertion or an unexpected localization of the spiral ganglion neurons might hinder the CI outcome, even in a patient with a genotype allowing residual transcriptional performance. Chao et al [ 29 ] also reported an inconsistent distribution and responsiveness of the residual spiral ganglion neuron in IP type III, with CI outcomes varying accordingly. Furthermore, a recent study showed that POU3F4 variants were associated with neurodevelopmental disorders, such as hyperactivity, concentration difficulties, poor phonological working memory, and slow language development [ 22 ], all of which may contribute to a negative CI outcome.…”

Considering gene therapy to protect from X‐linked deafness DFNX2 and associated neurodevelopmental disorders

“…In this sense, Smeds et al reported that very few DFNX2 children with cochlear implantation develop an age‐appropriate expressive language level and are rated to have adequate speech intellegibility 38,67 . Some studies also highlight the possibility that the benefits of implantation may decline over time (i.e., as the patient grows old) 11,14 . Choi et al 14 reported poorer auditory perception scores in DFNX2 patients 2 years after implantation relative to age‐matched cochlear implant recipients without inner ear malformations.…”

Genetics of Inner Ear Malformations: A Review

“…It is supposed to be the least frequent among the incomplete partitions, accounting for 2% of them [45]. This anomaly causes a mixed hearing loss, frequently worsening over time, with initial benefit from a hearing aid, but eventually requires cochlear implantation [46].…”

“…frequently worsening over time, with initial benefit from a hearing aid, but eventually requires cochlear implantation [46].…”