X-linked Malformation Deafness: Neurodevelopmental Symptoms Are Common in Children With IP3 Malformation and Mutation in POU3F4

Smeds, Henrik; Wales, Jeremy; Karltorp, Eva; Anderlid, Britt‐Marie; Henricson, Cecilia; Asp, Filip; Anmyr, Lena; Lagerstedt‐Robinson, Kristina; Löfkvist, Ulrika

doi:10.1097/aud.0000000000001073

Cited by 15 publications

(28 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…POU3F4 encodes a POU-domain TF expressed in mesenchymal cells of the otic capsule, responsible for normal inner ear development [ 21 , 22 ]. POU3F4 mutant mice have reduced endocochlear potential and alterations in cochlear spiral ligament fibrocytes [ 23 ], leading to hearing impairment.…”

Section: Discussionmentioning

confidence: 99%

“…Despite numerous reports on CI in patients with POU3F4 variants, detailed information is lacking and the postoperative outcomes have been highly variable. Choi et al [ 25 ] and Smeds et al [ 22 ] reported that patients with POU3F4 variants had improved speech scores after implantation but the scores were still lower than those of age-matched cohorts without apparent cochlear anomalies. These results differ from those reported by Tian et al [ 27 ] and Kang et al [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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

Han

Lee

et al. 2022

Biomedicines

View full text Add to dashboard Cite

Sensorineural hearing loss is one of the most common inherited sensory disorders. Functional classifications of deafness genes have shed light on genotype- and mechanism-based pharmacological approaches and on gene therapy strategies. In this study, we characterized the clinical phenotypes and genotypes of non-syndromic deafness caused by transcription factor (TF) gene variants, one of the functional classifications of genetic hearing loss. Of 1280 probands whose genomic DNA was subjected to molecular genetic testing, TF genes were responsible for hearing loss in 2.6%. Thirty-three pathogenic variants, including nine novel variants, accounting for non-syndromic deafness were clustered in only four TF genes (POU3F4, POU4F3, LMX1A, and EYA4), which is indicative of a narrow molecular etiologic spectrum of TF genes, and the functional redundancy of many other TF genes, in the context of non-syndromic deafness. The audiological and radiological characteristics associated with the four TF genes differed significantly, with a wide phenotypic spectrum. The results of this study reveal the genetic load of TF gene alterations among a cohort with non-syndromic hearing loss. Additionally, we have further refined the clinical profiles associated with TF gene variants as a basis for a personalized, genetically tailored approach to audiological rehabilitation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Han

Lee

et al. 2022

Biomedicines

View full text Add to dashboard Cite

show abstract

“…SOX2 has also been implicated in nervous system development and its disruption can lead to profound deficits in cognition, vision, and motor function 50 . Interestingly, POU3F4 has primarily been implicated in the development of semicircular canals and inherited deafness [51][52][53][54] but has also been linked to deficits in cognition and mental health (including attention deficit hyperactivity and developmental language disorder) which are significantly comorbid with this form of deafness 55 . These non-auditory deficits are more profound than those observed in controls with other forms of deafness, suggesting that POU3F4 provides a common molecular aetiology underlying aspects of both central and peripheral nervous system development 56,57 .…”

Section: Discussionmentioning

confidence: 99%

Identification of cell type-specific gene targets underlying thousands of rare diseases and subtraits

Murphy

Gordon-Smith

Chapman

et al. 2023

Preprint

View full text Add to dashboard Cite

Rare diseases (RDs) are uncommon as individual diagnoses, but as a group contribute to an enormous disease burden globally. However, partly due the low prevalence and high diversity of individual RDs, this category of diseases is understudied and under-resourced. The advent of large, standardised genetics databases has enabled high-throughput, comprehensive approaches that uncover new insights into the multi-scale aetiology of thousands of diseases. Here, using the Human Phenotype Ontology (9,677 annotated phenotypes) and multiple single-cell transcriptomic atlases (77 human cell types and 38 mouse cell types), we conducted >688,000 enrichment tests (x100,000 bootstrap iterations each) to identify >13,888 genetically supported cell type-phenotype associations. Our results recapitulate well-known cell type-phenotype relationships, and extend our understanding of these diseases by pinpointing the genes linking phenotypes to specific cell (sub)types. We also reveal novel cell type-phenotype relationships across disparate branches of clinical disease (e.g. the nervous, cardiovascular, and immune systems). Next, we introduce a computational pipeline to prioritise gene targets with high cell type-specificity to minimise off-target effects and maximise therapeutic potential. To broaden the impact of our study, we have released two R packages to fully replicate our analyses, as well as a series of interactive web apps so that stakeholders from a variety of backgrounds may further explore and utilise our findings. Together, we present a promising avenue for systematically and robustly uncovering the multi-scale aetiology of RDs at scale.

show abstract

“…Incomplete partition type III is the only malformation of the inner ear for which X-linked inheritance linked to the mutation of the POU3F4 gene is recognized (28). It is characterized by a normal external morphology of the cochlea with the absence of internal architecture, in particular the modiolus and the bottom of the internal auditory canal are absent.…”

Section: Incomplete Partition Type IIImentioning

confidence: 99%

Vestibular anomalies and dysfunctions in children with inner ear malformations: A narrative review

Brotto

Ariano²,

Sozzi³

et al. 2023

Front. Pediatr.

View full text Add to dashboard Cite

About 20% of children with congenital hearing loss present malformations of the inner ear. In the past few years much has been understood about the morphology and function of the anterior part of the labyrinth, since hearing loss may have a dramatic effect on the overall development of a child. Nowadays, for most of them, a chance for hearing rehabilitation is available, making hearing loss a treatable condition. The anomalies range from the lack of development of the whole inner ear to specific anomalies of isolated structures. Despite the frequent concomitant involvement of the posterior part of the labyrinth, this part of the inner ear is frequently neglected while discussing its morphology and dysfunction. Even though vestibular and balance function/dysfunction may have a significant impact on the global development of children, very little is known about these specific disorders in patients with inner ear malformations. The aim of this review is to summarize the available literature about vestibular anomalies and dysfunctions in children with inner ear malformations, discussing what is currently known about the topic.

show abstract

X-linked Malformation Deafness: Neurodevelopmental Symptoms Are Common in Children With IP3 Malformation and Mutation in POU3F4

Abstract: Supplemental Digital Content is available in the text.

Cited by 15 publications

References 89 publications

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

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

Identification of cell type-specific gene targets underlying thousands of rare diseases and subtraits

Vestibular anomalies and dysfunctions in children with inner ear malformations: A narrative review

Contact Info

Product

Resources

About