Type Of Deafness Research Articles

Emerging Concepts of Hearing Loss in Paget's Disease of Bone

Hearing loss has been recognized as a clinical feature of Paget’s disease of bone since Sir James Paget’s first case report (1). Involvement of the skull is commonly associated with involvement of the temporal bones and with hearing loss in Paget’s disease (2). An older concept that hearing loss in Paget’s disease is due to multiple mechanisms is giving way to a newer concept that there is a general mechanism causing hearing loss in most cases (3). Clinical and audiometric studies of hearing loss in Paget’s disease have described high-frequency sensorineural hearing loss and a low-frequency air–bone gap in most cases (4). (An air–bone gap indicates that auditory thresholds when measured by bone conduction are better than those predicted by air conduction thresholds.) An air–bone gap is usually interpreted as indicating a conductive type of deafness. Hearing levels have been shown to progress more rapidly in untreated Paget’s disease than in uncomplicated presbycusis (5). Histologic studies in the 1960s and 1970s showed a variety of derangements, including compression and stretching of the auditory nerve, microfractures of the otic capsule, loss of auditory hair cells and ganglion cells, invasion of labyrinthine spaces, and envelopment of ossicles by pagetic bone (4,6,7). More recently, histopathologic studies have also shown atrophy of the spiral ligament and endolymphatic hydrops (8). The presence of toxic cytokines has been shown in otosclerosis and suggested in Paget’s disease. Most of these data consist of histopathologic reports of advanced cases. On the other hand, the prominent histopathologist of the temporal bone, Harold F. Schuknecht, had long held the view that such dramatic findings were not the rule. He analyzed the largest group of histopathologic cases of Paget’s disease of the temporal bone to date in 1990 (9). Using a technique of graphic analysis that compared hearing levels in the range of the speech frequencies versus the loss of auditory hair cells and ganglion cells that carry the neural place code for each of those tones, he could not demonstrate any systematic relationships. Aside from the presence of pagetic bone, the specimens were typical for the age of the subjects. There were no findings that would explain the air-bone gap, such as fixation or disruption of the auditory ossicles.

Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F.

We have determined the molecular basis for Usher syndrome type 1F (USH1F) in two families segregating for this type of syndromic deafness. By fluorescence in situ hybridization, we placed the human homolog of the mouse protocadherin Pcdh15 in the linkage interval defined by the USH1F locus. We determined the genomic structure of this novel protocadherin, and found a single-base deletion in exon 10 in one USH1F family and a nonsense mutation in exon 2 in the second. Consistent with the phenotypes observed in these families, we demonstrated expression of PCDH15 in the retina and cochlea by RT-PCR and immunohistochemistry. This report shows that protocadherins are essential for maintenance of normal retinal and cochlear function.

Characterisation and genetic mapping of a new X linked deafness syndrome

BACKGROUNDHereditary forms of hearing loss are classified as syndromic, when deafness is associated with other clinical features, or non-syndromic, when deafness occurs without other clinical features. Many types of syndromic...

Connexin26 Mutations Associated With Nonsyndromic Hearing Loss

Mutations in the GJB2 gene are a major cause of autosomal recessive and sporadic types of congenital deafness. The 35delG mutation is the most frequent type of mutation in white populations. However, several other forms were reported, such as 167delT among Ashkenazi Jews and R143W in Africans. The present study investigated the mutations of connexin26 (Cx26) found in patients with nonsyndromic hearing loss (NSHL) and newborns in the Korean population. The sequencing data for 147 unrelated patients with congenital NSHL and 100 audiologically screened newborns were included in this prospective study. Genomic DNA samples from all patients and newborns were sequenced in both directions for detection of Cx26 mutations. Thirteen different types of mutations were found in the patients and newborns. V27I and E114G are the popular types of polymorphic mutations in both groups. 235delC-deletion and frameshift--was detected in patients (15 in 294 alleles) and newborns (1 in 200 alleles). 35delG was rarely found in both group. In addition to above mutations, several types of mutations--S85P, K41R, S72C, V84A, 176-191del, and 299-300del-were identified. The family study of the 235delC showed a typical autosomal recessive trait of NSHL in their audiological evaluation of hearing threshold. The frequency of 235delC allele showed much higher in the patients (5%) than in newborns (0.5%). We rarely found 35delC mutant in both groups. These results suggest that the different types of Cx26 mutations affect autosomal recessive NSHL according to ethnic background.

Analysis of a cohort of children with sensory hearing loss using the SCALE systematic nomenclature.

What characteristics identify clinical types of childhood deafness? Which aspects of the otological evaluation best delineate them? To approach these related questions, a classification for deafness consistent with current medical concepts was constructed using a systematic nomenclature and then applied to a pediatric cohort of 168 children with sensorineural hearing loss (SNHL) who were referred for private consultation. A major aim of the analysis was to test the utility of SCALE, the new systematic nomenclature. Patients with SNHL were identified through the office records of a single faculty member of the Department of Otolaryngology in a medical school situated in a major US city. Inclusion criteria required bone conduction thresholds above 30 dB or equivalent in at least one of the frequencies from 250 Hz to 4 kHz on either behavioral audiogram or on electrophysiological testing. All identified patients had initial visits during an 8-year period from late 1990 to early 1999. Patients were excluded if age at first consultation was 19 years or more, if records were insufficient to confirm SNHL, or if further evaluation revealed that SNHL had been misdiagnosed. A formal nomenclature was designed to systematically encode clinical features with simple descriptive terms according to an acronym (SCALE [sidedness, component function, age of onset, lesion, and etiology]) for all included patients. One hundred sixty-eight study patients were analyzed; sensory hearing loss was bilateral in 82% (137/168) and unilateral in 18% (31/168). The etiology of this impairment was determined to be intrinsic in 40% of children (67/168), either secondary to genotype (57/ 67), or to named congenital syndromes without known extrinsic cause (10/67). Recessive single gene mutations diagnosed by family history, recognition of syndrome, or determination of homozygous 35delG mutations in the gap junction protein gene, Connexin 26, accounted for bilateral sensory hearing loss in 33 children (24% of all bilateral cases). One girl had an X-linked dominant syndrome (Coffin-Lowry syndrome) with auditory brainstem response-documented childhood onset of SNHL. Nine patients (5%) had chromosomal aneuploidy, and 12 patients (7%) had either a family history of dominant deafness (7/ 12) or a recognizable autosomal dominant syndrome (5/12), most commonly, Waardenburg syndrome type 1 (4/5). Extrinsic causes of deafness were identified in only 13% of children (21/168) and included a relatively large number of referrals from neurosurgery (9/21). Three of these children had chronic middle ear disease and sensory hearing loss associated with inflammatory and bony changes on temporal bone imaging suggestive of chronic osteitis; all had a history of active otitis media during cranial irradiation. Congenital cytomegalovirus infections were documented in only 4 cases, but 41 patients could have had this as a cause or did not have this cause ruled out. An idiopathic cause or origin was assigned to 36% of patients (61/168) including patients with unnamed syndromic patterns of multiple anomalies. The SCALE nomenclature facilitated complete descriptions of hearing-impaired children and provided a classification scheme applicable to broad categories of human disease. The single most useful diagnostic test was screening for Cx26 mutations. Computed tomography scan of the temporal bones was helpful in establishing etiology for selected patients and invaluable in patients with chronic ear disease. Magnetic resonance imaging scan was a superior diagnostic modality in one child with a posterior fossa arachnoid cyst.

遅発性内リンパ水腫について 特にメニエール病との関連

Delayed endolymphatic hydrops (DEH), a disease entity that can be differentiated from Meniere's disease, typically develops in patients who have experienced a profound, long-term hearing loss in one ear. This condition was first reported by Kamei et al. ('71), who indicated that it occurred in about 20% of patients who had had unilateral profound deafness since early childhood (UPDC), and it appeared at various stages of adulthood, during or after puberty. Wolfson and Leiberman ('75) and Nadol et al. ('75) reported other types of unilateral profound deafness causing this condition that were due to viral and bacterial labyrinthitis, head trauma, or sudden deafness. Schuknecht ('78) defined DEH and classified it into two types: the ipsilateral type, in which vestibular symptoms identical to the vestibular symptoms of Meniere's disease develop in a previously deafened ear, and the contralateral type, in which a fluctuating hearing loss and/or vestibular symptoms develop in the hearing ear. The underlying pathophysiologic mechanism for the development of DEH has been explained as progressive endolymphatic hydrops in the inner ear due to delayed atrophy or fibrous obliteration of the endolymphatic resorption system, resulting from a previous inner-ear injury. In the ipsilateral type, episodic vertigo is not usually accompanied by fluctuating hearing levels and tinnitus because the hearing loss is profound. The period between the onset of pre-existent deafness in one ear and the onset of DEH ranges from several months to 74 years. The cause of the pre-existent deafness is UPDC in more than half of the cases of both types of DEH. Almost all kinds of other degenerative disorders of the inner ear are mostly due to inflammation (viral and bacterial) and trauma (physical and acoustic). The ipsilateral type of DEH is more frequently seen than the contralateral type. The onset age of the contralateral type is higher, in general, than that of the ipsilateral type. Medical treatment may be effective for both types of DEH. Complete relief from episodic recurrent vertigo may be expected in 65% of cases within 5 years after the onset of vertigo and in 90% of cases within 10 years. Labyrinthectomy or vestibular nerve section in the deaf ear is curative in the ipsilateral type, but no satisfactory surgical therapy is available for the contralateral type of the disease. The audiological definition of DEH by Schuknecht seems, however, to be somewhat arbitrary, as the patients' symptoms form a continuous spectrum with other Meniere's syndrome cases, occurring in association with less-marked degrees of sensorineural hearing loss. The existence of the contralateral type of DEH due to UPDC, which often shows typical symptoms of Meniere's disease, seems to suggest that Meniere's disease may occur as a delayed sequela of subclinical damage of the inner ear, especially damage sustained in childhood.

GJB2 Gene Mutations in Childhood Deafness

The frequency of childhood deafness is estimated at 1:1,000 and at least half of these cases are genetic. Recently, mutations in the GJB2 gene have been found in a great number of familial and sporadic cases of congenital deafness in Caucasians. The most common mutation (70%) is the frameshift mutation of a single guanine in position 35 (35delG). More than 20 mutations in the GJB2 gene are associated with DFNB1, a prevalent type of autosomal recessive non-syndromic neurosensory deafness. Last year we initiated a systematic screening programme to evaluate the causes of deafness in the population of prelingually deaf children who are referred to our cochlear implant programme. All of the deaf children and their parents undergo a comprehensive medical review, directed to identify causes of acquired deafness and manifestations of syndromic hearing impairment. DNA is extracted from the blood of all of the children. The technique AS-PCR (allele-specific polymerase chain reaction) is used for the identification of the mutation 35delG. Screening for other GJB2 gene mutations is carried out by single-strand conformation polymorphisms (SSCP). Our results on the identification of DFNB1 will be presented, as well as a discussion on the implications of an aetiological diagnosis in cochlear implantation.

The ins and outs of X-linked deafness type 3.

The ins and outs of X-linked deafness type 3.

A Novel Ribosomal S6-Kinase (RSK4; RPS6KA6) Is Commonly Deleted in Patients with Complex X-Linked Mental Retardation

Large deletions in Xq21 often are associated with contiguous gene syndromes consisting of X-linked deafness type 3 (DFN3), mental retardation (MRX), and choroideremia (CHM). The identification of deletions associated with classic CHM or DFN3 facilitated the positional cloning of the underlying genes, REP-1 and POU3F4, respectively, and enabled the positioning of the MRX gene in between these genes. Here, we report the cloning and characterization of a novel gene, ribosomal S6-kinase 4 (RSK4; HGMW-approved symbol RPS6KA6), which maps in the MRX critical region. RSK4 is completely deleted in eight patients with the contiguous gene syndrome including MRX, partially deleted in a patient with DFN3 and present in patients with an Xq21 deletion and normal intellectual abilities. RSK4 is most abundantly expressed in brain and kidney. The predicted protein of 746 amino acids shows a high level of homology to three previously isolated members of the human RSK family. RSK2 is involved in Coffin–Lowry syndrome and nonspecific MRX. The localization of RSK4 in the interval that is commonly deleted in mentally retarded males together with the high degree of amino acid identity with RSK2 suggests that RSK4 plays a role in normal neuronal development. Further mutation analyses in males with X-linked mental retardation must prove that RSK4 is indeed a novel MRX gene.

Confirmation of deafness in infancy

AIMTo assess delay in confirming hearing impairment in infants identified by universal neonatal screening and to investigate the causes.PATIENTSInfants identified from 25 199 babies screened from January 1992 to December...

A STEPWISE APPROACH TO THE DIAGNOSIS AND TREATMENT OF HEREDITARY HEARING LOSS

What To Do Do suspect a genetic cause in all cases of hearing loss. Do develop a working knowledge of common types of HHI that you may draw on to aid in diagnosis. Do think of HHI when the audiogram reveals a hearing loss with a "cookie bite" configuration. Do refer the infant to a geneticist in cases where you suspect a syndromic HHI, a nonsyndromic HHI, and in cases of "cryptogenic" hearing loss where an underlying HHI may be present. Often, the associated symptoms are subtle and best detected by a professional who deals with these issues on a daily basis. Do get the infant or family plugged into an audiologist or otolaryngologist and speech pathologist who will preferably work as a team to maximize aural rehabilitation and ensure serial follow-up. It is never too early to fit a child with hearing aids. Do refer to the HHIRR center at Boys Town. Do refer to the correct "deaf" organization or "blind-deaf" organization. Do think about working up other siblings or family members. Do keep in mind that some members of the "deaf society" may regard deafness as an alternative lifestyle and may not be amenable to their child's referral for additional workup and aural rehabilitation. What Not To Do Do not assume the child is deaf and nothing can be done. Do not wait until the child is older to refer to an otolaryngologist, speech therapist, and audiologist. Do not order a sonogram. Do not order a temporal bone CT scan on newborns. Do not forget about other siblings who may have a similar pathology. Do not forget that some forms of HHI can present beyond infancy. The pediatrician is the front line and can play a major role in the diagnosis, workup, and treatment of HHI. Armed with the proper degree of suspicion, careful elicitation of family history, meticulous physical examination, evaluation of the audiogram, and adequate fund of knowledge of common types of genetic deafness, the pediatrician can make a timely diagnosis and appropriate referrals. This avoids delay in detection of significant hearing impairment and the associated lack of essential skills in speech, language, and social interaction. No child is too young to have some type of hearing assessment. Early detection and intervention are best done with a multidisciplinary team approach with a neonatologist or pediatrician, audiologist, speech therapist, and otolaryngologist. In the future, blood tests using genetic probes may be available to screen for many types of HHI.

Making connections with mitochondria?

Two recent papers have revealed a remarkable involvement of a single human gene, GJB3, in two apparently distinct disorders: progressive hearing loss 1 X J.H. et al. Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment. Nat. Genet. 1998; 20: 370-373 Crossref PubMed Scopus (380) Google Scholar and a form of hyperkeratosis, Erythrokeratodermia variabilis2 Richard G. et al. Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis. Nat. Genet. 1998; 20: 366-369 Crossref PubMed Scopus (299) Google Scholar . The gene encodes connexin 31, a member of a large family of gap junction-forming proteins, two other members of which have already been implicated in both dominant and recessive forms of syndromic and non-syndromic deafness. The precise mechanisms by which different connexin mutations produce these two pathological phenotypes remain to be elucidated, but a further remarkable connection between deafness and a hyperkeratotic disorder is provided by the NP7445 mitochondrial DNA mutation. Sevior et al.3 Sevior K.B. et al. Mitochondrial A7445G mutation in two pedigrees with palmoplantar keratoderma and deafness. Am. J. Med. Genet. 1998; 75: 179-185 Crossref PubMed Scopus (118) Google Scholar found that this mutation was associated with a combined phenotype of progressive hearing loss and palmoplantar keratoderma in two different maternal pedigrees, one from New Zealand, the other from Japan. The same applies to the Scottish family in which the mutation was first reported (G.A. Vernham et al., unpublished), indicating that the association is robust. Mutations in connexins and in mtDNA can result in superficially similar types of deafness, although no detail on the exact cellular or developmental abnormalities arising from either is yet available. The fact that both are also associated with forms of hyperkeratosis strongly suggests a common mechanism. One possibility is that various types of epithelial cell function or patterning require propagation of an ionic signal across a cell sheet, an obvious candidate being calcium. Gap junctions would transmit such a signal between cells, whereas properly energized mitochondria would be required to transmit the signal across each single cell. It is already known that mitochondria can transduce and amplify calcium waves across cells in a manner dependent on respiratory energy 4 Ichas F. et al. Mitochondria are excitable organelles capable of generating and conveying electrical and calcium signals. Cell. 1997; 89: 1145-1153 Abstract Full Text Full Text PDF PubMed Scopus (646) Google Scholar . Even if this hypothesis is correct, many mysteries remain, not least of which is the question of why only a subset of mtDNA mutations affecting protein synthesis results in deafness, and why only one, so far, is involved also in hyperkeratosis. Until recently, this type of feature was widely regarded as a peculiarity of mitochondrial genetics. The connexin phenotypes illustrate the fact that this is really a more general property of human disease mutations.

An Analysis of a Large Postlingually Deaf Family with Hereditary Non-syndromic Profound Hearing Loss

We initiated a clinical and genetic linkage study on members of a large Venezuelan family with hereditary hearing loss. A medical history and a physical examination were performed on 30 family members. Audiometry was carried out in 25 subjects, and in 2 additional children auditory brainstem responses were obtained. Additional testing (site-of-lesion, electronystagmography and computed tomography) was also obtained in a few subjects. DNA was extracted from blood samples from 25 family members. The type of deafness in this family is neurosensorial, non-syndromic and postlingual. The average age of onset of deafness is 7 years and there is a rapid progression leading to profound deafness. Deafness is possibly of cochlear origin and there is no associated vestibular pathology. Analysis of the pedigree discloses a maternal pattern of inheritance with a significant female predominance, compatible with a mutation of the mitochondrial DNA. The molecular DNA analysis for the known mitochondrial mutations are discussed.

Editorial

Editorial Genetic Engineering and Our Brave New World Advances in the fields of genetics and molecular biology seem to occur on a daily basis, with particular attention to the Human Genome Project of the National Institutes of Health and the Department of Energy, which is involved in the mapping of the approximately 80,000 human genes. The possibilities and implications are breath-taking. For the first time in our existence there is the potential, in the near future, of genetically changing the human "germ line." By altering the composition of sperm and eggs before conception, we may be able to redirect the course of evolution. There have already been significant breakthroughs in the area of hereditary hearing loss. In 1994, Couke and colleagues reported that, by studying a large Indonesian family with many deaf and hearing members, they were able to localize the gene for a specific type of deafness. They then performed chromosomal analysis with two other families and in one family established linkage in the same chromosomal area. Although, to the best of my knowledge , the specific gene has not been isolated, gene mapping studies will ultimately lead to the identification of the gene and determination of its structure and function (Arnos, 1994). Since 1994 advances have been made in several countries, including the United States, Great Britain , Israel, and Italy. Most recently, Steele (1998) reported on research in Great Britain on detection of a gene related to progressive hearing loss, declaring that detection of such a gene could lead to procedures that could repress properties that cause a progressive hearing loss. She concluded that time is running out on progressive hearing loss and that a molecular understanding and intervention strategy may be closer than we think. Steele's projections may or may not be overly optimistic , since there are at least 200 types of hereditary hearing loss. Success is being reported on the more easily identifiable cases. However, there is little doubt that the major portion of the Human Genome Project will be completed within the life-times of most readers. The most obvious application of genetic engineering is in the eradication of human disorders such as diabetes, sickle-cell anemia, and certain types of cancer. Few people would argue with such efforts to reduce human suffering. Within the framework of traditional eugenics this would fall within the domain of "Negative Eugenics," the systematic elimination of undesirable traits. The second application would entail the concept of "Positive Eugenics" to improve the characteristics of the human race. We are all aware of the selective breeding of plants and animals designed to improve or emphasize the characteristics of various species. In the case of human beings, for centuries there have been concerns expressed that the "better" classes in a particular society were being outbred by the "lower" classes. We are also aware of the horrific effects of both kinds of eugenics in Nazi Germany, which combined efforts to breed "pure Aryans" with efforts to destroy entire groups of "Untermenschen"; from Jews and Gypsies to deaf, gay, and retarded individuals. Recent developments are raising serious practical, moral, and ethical issues that will have to be dealt with for generations to come (Moores, 1996). In terms of "negative" genetics — the elimination of undesirable traits — most people would probably agree that elimination of cancer and sickle-cell anemia is desirable. The question is where should it end, where should we draw the line? Rifkin (1998) asks if cancer can be prevented by altering the genetic codes of individuals, why not proceed to less serious "disorders" such as color blindness, dyslexia, obesity, and short stature? If we spend billions on dollars on Rogaine to regrow hair, on psychotropic drugs to alter moods, and on liposuction and chin-tucks, many of us would be ready to use gene therapy to enhance the population . He cites a poll in which 43% of Americans would approve using gene therapy to improve children's physical characteristics. What constitutes an improvement is a moot point. The scope of this editorial and space limitations preclude addressing "genetic enhancement" and the more complex issues of "negative eugenics." I just want to raise a few issues related to genetic hearing loss...

Progressive Sensorineural Hearing Loss and a Widened Vestibular Aqueduct in Pendred Syndrome

Pendred syndrome is an autosomal recessive inherited disorder. Obligatory features are profound deafness in childhood and defective organic binding of iodine in the thyroid gland. Therefore, goiter is a common symptom. Hypoplasia of the cochlea is another feature. Recently, the gene for Pendred syndrome was identified. We describe a boy whose sensorineural hearing loss in both ears progressed rapidly from about 50 to 60 dB at the age of 3 years and 3 months to more than 100 dB at the age of 4 years and 4 months. This loss was preceded by a medical history of a progressive hearing loss. The progressive nature of the hearing loss motivated a search for the cause. Dysplasia of the cochlea and a widened vestibular aqueduct were found. The results of thyroid function tests were normal, but he had an elevated level of thyroglobulin. The diagnosis of Pendred syndrome was confirmed by the positive results of a potassium perchlorate test, indicating defective organic binding of iodine in the thyroid gland. It is possible that the widened vestibular aqueduct was responsible for the increase in the hearing impairment. Aside from the branchio-otorenal syndrome, Pendred syndrome is the only other known genetic disorder with a widened vestibular aqueduct. If a child has progressive sensorineural deafness and a widened vestibular aqueduct, it is important to consider a diagnosis of Pendred syndrome. A widened vestibular aqueduct may help to elucidate the pathophysiologic characteristics of hearing loss in these genetic types of deafness in childhood.

Novel Mutations in the Connexin 26 Gene (GJB2) That Cause Autosomal Recessive (DFNB1) Hearing Loss

Mutations in the connexin 26 (Cx26) gene (GJB2) are associated with the type of autosomal recessive nonsyndromic neurosensory deafness known as "DFNB1." Studies indicate that DFNB1 (13q11-12) causes 20% of all childhood deafness and may have a carrier rate as high as 2. 8%. This study describes the analysis of 58 multiplex families each having at least two affected children diagnosed with autosomal recessive nonsyndromic deafness. Twenty of the 58 families were observed to have mutations in both alleles of Cx26. Thirty-three of 116 chromosomes contained a 30delG allele, for a frequency of .284. This mutation was observed in 2 of 192 control chromosomes, for an estimated gene frequency of .01+/-.007. The homozygous frequency of the 30delG allele is then estimated at .0001, or 1/10,000. Given that the frequency of all childhood hearing impairment is 1/1,000 and that half of that is genetic, the specific mutation 30delG is responsible for 10% of all childhood hearing loss and for 20% of all childhood hereditary hearing loss. Six novel mutations were also observed in the affected population. The deletions detected cause frameshifts that would severely disrupt the protein structure. Three novel missense mutations, Val84Met, Val95Met, and Ser113Pro, were observed. The missense mutation 101T-->C has been reported to be a dominant allele of DFNA3, a dominant nonsyndromic hearing loss. Data further supporting the finding that this mutation does not cause dominant hearing loss are presented. This allele was found in a recessive family segregating independently from the hearing-loss phenotype and in 3 of 192 control chromosomes. These results indicate that 101T-->C is not sufficient to cause hearing loss.

Genetic causes of hearing loss.

In the past year, genes involved in the branchio-oto-renal and Treacher-Collins syndromes were cloned. Myosin 7A, a gene previously implicated in Usher syndrome type 1B, was also found to be mutated in non-syndromic hearing loss. Likewise, linkage studies in Pendred syndrome and Usher syndrome type 1D suggest that allelic mutations can cause syndromic and non-syndromic forms of deafness. In patients with X-linked deafness type 3, a hotspot for deletions was found 900 kb proximal to the causal gene POU3F4. Most importantly, the connexin 26 gene is mutated in approximately 50% of all recessive deafness families, enabling early diagnosis and carrier detection.

低音障害型感音難聴に対するイソソルビド有効例の早期選別について

低音障害型感音難聴に対するイソソルビド有効例の早期選別について

The molecular basis of X‐linked deafness type 3 (DFN3) in two sporadic cases: Identification of a somatic mosaicism for a POU3F4 missense mutation

The molecular basis of X‐linked deafness type 3 (DFN3) in two sporadic cases: Identification of a somatic mosaicism for a POU3F4 missense mutation

聾型突発性難聴の聴力予後の検討

聾型突発性難聴の聴力予後の検討