Deletion of and novel missense mutation in POU3F4 in 2 families segregating X-linked nonsyndromic deafness

Abram P Vore; Eugene H Chang; Jane E Hoppe; Merlin G Butler; Shawnia Forrester; Michael C Schneider; Luke L H Smith; Daniel W Burke; Colleen A Campbell; Richard J H Smith

doi:10.1001/archotol.131.12.1057

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Deletion of and novel missense mutation in POU3F4 in 2 families segregating X-linked nonsyndromic deafness

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Deletion of and novel missense mutation in POU3F4 in 2 families segregating X-linked nonsyndromic deafness

Abram P Vore, Eugene H Chang, Jane E Hoppe, Merlin G Butler, Shawnia Forrester, Michael C Schneider, Luke L H Smith, Daniel W Burke, Colleen A Campbell and Richard J H Smith

Archives of otolaryngology--head & neck surgery, Vol.131(12), pp.1057-1063

12/2005

DOI: 10.1001/archotol.131.12.1057

PMCID: PMC6775642

PMID: 16365218

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Abstract

To analyze the physical manifestations and genetic features of 2 families segregating X-linked deafness, which is most commonly reported to be caused by mutations of the POU domain gene POU3F4 at the DFN3 locus. Computed tomographic study of the temporal bone in probands from each family, followed by mutation screening and deletion mapping of POU3F4 in family members. Two midwestern genetics clinics. Two families with X-linked deafness. Anomalies of the inner ear in the probands; results of gene mapping and severity and effects of hearing loss in the family members. In the first family, a large deletion was identified that includes POU3F4 and extends upstream approximately 530 kilobases; in the second family, a novel serine-to-leucine (S228L) amino acid mutation was identified in the POU-specific domain of POU3F4. Both the deletion and the missense mutation segregate with the clinical phenotype and are causally related to the deafness in these families. Deafness related to the POU3F4 gene is associated with dilation of the internal auditory canal and a spectrum of other temporal bone anomalies that range in severity from mild to severe dysplasia of the cochlea and semicircular canals. The consequence of these anomalies is a congenital mixed hearing loss, the sensorineural component of which progresses over time. Affected males can also present with vestibular dysfunction that is associated with delayed developmental motor milestones. Intrafamilial variability occurs.

Chromosome Deletion

Chromosome Segregation

Temporal Bone - diagnostic imaging

Deafness - genetics

Sensory Thresholds

Humans

Serine - genetics

Male

Tomography, X-Ray Computed

Leucine

Mutation, Missense

POU Domain Factors - genetics

Pedigree

Female

Genetic Diseases, X-Linked - genetics

Details

Title: Subtitle: Deletion of and novel missense mutation in POU3F4 in 2 families segregating X-linked nonsyndromic deafness
Creators: Abram P Vore - Molecular Otolaryngology Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, The University of Iowa, Iowa City 52242, USA
Eugene H Chang
Jane E Hoppe
Merlin G Butler
Shawnia Forrester
Michael C Schneider
Luke L H Smith
Daniel W Burke
Colleen A Campbell
Richard J H Smith
Resource Type: Journal article
Publication Details: Archives of otolaryngology--head & neck surgery, Vol.131(12), pp.1057-1063
DOI: 10.1001/archotol.131.12.1057
PMID: 16365218
PMCID: PMC6775642
NLM abbreviation: Arch Otolaryngol Head Neck Surg
ISSN: 0886-4470
eISSN: 1538-361X
Publisher: American Medical Association; United States
Grant note: R01 DC03544 / NIDCD NIH HHS
Language: English
Date published: 12/2005
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Cardiovascular Medicine; Otolaryngology; Internal Medicine
Record Identifier: 9984006369402771

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