Sex‐linked deafness

Petersen, MB; Wang, Q; Willems, P. J.

doi:10.1111/j.1399-0004.2007.00913.x

Cited by 67 publications

(84 citation statements)

References 77 publications

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“…DFN3 is 1 of 4 Xlinked loci implicated in congenital deafness (the others being DF2, DF4, and DF6) and has been found in approximately 50% of families with X-linked hearing loss. 22 Symptomatic patients with this mutation are typically male and present with hearing loss at birth, which rapidly progresses to severe deafness within the first decade. Hearing loss is typically mixed, but some individuals demonstrate SNHL without a conductive component.…”

Section: X-linked Deafness With Stapes Gushermentioning

confidence: 99%

“…Vestibular problems are also common in these patients. 22 Female carriers of the gene mutation may have normal hearing or only mild-to-moderate hearing loss. 23 In patients with the DFN3 mutation, there is a communication between the subarachnoid and perilymphatic spaces due to deficiency of the lamina cribrosa separating the IAC from the basal turn of the cochlea.…”

Section: X-linked Deafness With Stapes Gushermentioning

confidence: 99%

See 1 more Smart Citation

Pediatric Sensorineural Hearing Loss, Part 2: Syndromic and Acquired Causes

Huang¹,

Zdanski²,

Castillo³

2011

AJNR Am J Neuroradiol

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SUMMARY:This article is the second in a 2-part series reviewing neuroimaging in childhood SNHL. Previously, we discussed the clinical work-up of children with hearing impairment, the classification of inner ear malformations, and congenital nonsyndromic causes of hearing loss. Here, we review and illustrate the most common syndromic hereditary and acquired causes of childhood SNHL, with an emphasis on entities that demonstrate inner ear abnormalities on cross-sectional imaging. Syndromes discussed include BOR syndrome, CHARGE syndrome, Pendred syndrome, Waardenburg syndrome, and X-linked hearing loss with stapes gusher. We conclude the article with a review of acquired causes of childhood SNHL, including infections, trauma, and neoplasms.ABBREVIATIONS: BOR ϭ branchio-oto-renal; CISS ϭ constructive interference in steady state; IAC ϭ internal auditory canal; NF-2 ϭ neurofibromatosis type II; SCC ϭ semicircular canal; SNHL ϭ sensorineural hearing loss; T1WI ϭ T1-weighted image; T2WI ϭ T2-weighted image T he estimated prevalence of SNHL in patients younger than 18 years of age is 6 per 1000, 1 making it one of the leading causes of childhood disability and a common reason for otolaryngology referrals. Cross-sectional imaging is now routinely performed in these patients because it provides important information about potential etiologies for hearing loss, defines the anatomy of the temporal bone and the central auditory pathway, and identifies additional intracranial abnormalities that may require further work-up. In the first part of our series, we reviewed some of the practical aspects related to imaging children with SNHL, including epidemiology, clinical work-up, and choices of imaging technique; we also discussed the classification of congenital inner ear malformations and congenital nonsyndromic causes of SNHL. In this article, we continue our discussion of neuroimaging for childhood SNHL, focusing on several of the most common syndromic hereditary forms of SNHL as well as acquired causes of hearing loss.

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Section: X-linked Deafness With Stapes Gushermentioning

confidence: 99%

Section: X-linked Deafness With Stapes Gushermentioning

confidence: 99%

Pediatric Sensorineural Hearing Loss, Part 2: Syndromic and Acquired Causes

Huang¹,

Zdanski²,

Castillo³

2011

AJNR Am J Neuroradiol

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“…As a result of the widening of the bony IAC, cerebrospinal fluid can enter the vestibule, which is thought to underlie the reported "gusher" phenomenon, described as fluid gushing out upon removal of the stapes footplate during corrective surgery (8). Female carriers of a mutation in the DFN3 locus typically show little or no hearing loss (26).Deafness segregating at the DFN3 locus is associated with mutations in the POU3F4 gene (11). POU3F4 belongs to a superfamily of POU domain transcription factors, which are characterized by a conserved bipartite DNA binding domain.…”

mentioning

confidence: 99%

Clinical and molecular characterizations of novelPOU3F4mutations reveal that DFN3 is due to null function of POU3F4 protein

Lee

Song

Kang

et al. 2009

Physiological Genomics

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UK. Clinical and molecular characterizations of novel POU3F4 mutations reveal that DFN3 is due to null function of POU3F4 protein. Physiol Genomics 39: 195-201, 2009. First published August 11, 2009 doi:10.1152/physiolgenomics.00100.2009.-X-linked deafness type 3 (DFN3), the most prevalent X-linked form of hereditary deafness, is caused by mutations in the POU3F4 locus, which encodes a member of the POU family of transcription factors. Despite numerous reports on clinical evaluations and genetic analyses describing novel POU3F4 mutations, little is known about how such mutations affect normal functions of the POU3F4 protein and cause inner ear malformations and deafness. Here we describe three novel mutations of the POU3F4 gene and their clinical characterizations in three Korean families carrying deafness segregating at the DFN3 locus. The three mutations cause a substitution (p.Arg329Pro) or a deletion (p.Ser310del) of highly conserved amino acid residues in the POU homeodomain or a truncation that eliminates both DNA-binding domains (p.Ala116fs). In an attempt to better understand the molecular mechanisms underlying their inner ear defects, we examined the behavior of the normal and mutant forms of the POU3F4 protein in C3H/10T1/2 mesodermal cells. Protein modeling as well as in vitro assays demonstrated that these mutations are detrimental to the tertiary structure of the POU3F4 protein and severely affect its ability to bind DNA. All three mutated POU3F4 proteins failed to transactivate expression of a reporter gene. In addition, all three failed to inhibit the transcriptional activity of wild-type proteins when both wildtype and mutant proteins were coexpressed. Since most of the mutations reported for DFN3 thus far are associated with regions that encode the DNA binding domains of POU3F4, our results strongly suggest that the deafness in DFN3 patients is largely due to the null function of POU3F4. hearing loss; X-linked deafness type 3; inner ear CONGENITAL HEARING LOSS IS one of the most common sensory disorders in humans, affecting approximately one in 1,000 newborns (24). More than 50% of the congenital hearing loss is due to genetic causes, and the majority of these hereditary cases are nonsyndromic. While most genetic nonsyndromic hearing loss is caused by mutations in autosomal genes, X-linked cases are estimated to comprise between 1 and 5% of these (26). Thus far, four different X-linked nonsyndromic hearing loss loci (DFN2, DFN3, DFN4, and DFN6) have been mapped, but the causative gene has been identified only for the DFN3 locus (33).X-linked deafness type 3 (DFN3) accounts for ϳ50% of all families carrying X-linked nonsyndromic hearing loss (26). Clinical characteristics of DFN3 in affected males include temporal bone abnormalities, stapes fixation, and, in most cases, a mixed type of hearing loss, which is often progressive (7,8,10). Anatomical anomalies of the temporal bone revealed by computer-assisted tomography (CT) include dilatation of the lateral end of the internal acoustic canal (IAC...

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“…76 This gene plays key roles in mesenchymal differentiation into fibrocytes during cochlear development, 24 and its mutations cause X-linked deafness of type 2 (DFNX2). 76 The latter accounts for ~50% of all families with X-linked nonsyndromic hearing loss 77 and is clinically characterized by bilateral, progressive, and mixed conductive-sensorineural hearing loss. Moreover, this disease is accompanied by temporal-bone anomalies, stapedial fixation, and perilymphatic gusher during stapes surgery.…”

Section: Fibrocytic Differentiationmentioning

confidence: 99%