Yuya Tamagawa

Phenotype of DFNA11: A Nonsyndromic Hearing Loss Caused by a Myosin VIIA Mutation

Objectives/Hypothesis To characterize the audiovestibular phenotype of DFNA11, an autosomal dominant nonsyndromic hearing impairment caused by a mutation in the myosin VIIA gene (MYO7A), including whether DFNA11‐affected subjects have retinal degeneration as is characteristic of Usher syndrome type 1B, caused by different MYO7A mutations.

Audiologic Findings in Patients with a Point Mutation at Nucleotide 3,243 of Mitochondrial Dna

A mitochondrial tRNALeu(UUR) mutation at nucleotide 3,243 is known to be found in most patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) and has also been identified in several families with maternally inherited diabetes mellitus and hearing loss. We report here audiologic features in patients with hearing loss associated with the mutation. Four patients without and five with MELAS were studied. Most of the patients had bilateral progressive sensorineural hearing loss. The most common shape of the audiogram was sloping, while cases in the advanced stages had flat audiograms. Speech discrimination scores were generally poor and did not parallel the degree of hearing loss. The present study suggests that the lesion for hearing loss could include both cochlear and retrocochlear involvement, but does not demonstrate a significant difference in the audiologic findings between patients with and without MELAS.

Nonsyndromic hearing loss caused by a mitochondrial T7511C mutation

Objectives The aims of the present study were to identify a mutation in a Japanese family showing nonsyndromic sensorineural hearing loss and to relate the mutation to characteristics of patients, including audiovestibular findings.

Temporal bone histopathological and quantitative analysis of mitochondrial DNA in MELAS.

Objectives/Hypothesis Although hearing loss is common in MELAS (syndrome of mitochondrial encephalopathy, lactic acidosis and stroke‐like episodes), the histopathology of the temporal bone has not been reported. The majority of cases of MELAS are linked to a mitochondrial DNA (mtDNA) mutation at nucleotide 3243. In MELAS, normal mtDNA and mutant mtDNA coexist in a heteroplasmic manner. The purpose of the study was to report the otopathological findings from two patients with MELAS and quantitative mtDNA analysis in the inner ear of one of these patients.

Mutations of the Pendred syndrome gene (PDS) in patients with large vestibular aqueduct

A recent report demonstrated the presence of a mutation in the Pendred syndrome gene (PDS) of patients with large vestibular aqueducts but without goitre. We studied PDS mutations in members of four Japanese families, among which five affected members showed bilateral enlarged vestibular aqueducts. All affected members exhibited moderate to severe bilateral fluctuating sensorineural hearing loss and the absence of goitre. Three members also suffered from recurrent episodic vertiginous spells. Analysis of PDS mutation revealed two single base changes (mis-sense mutations) in exons 19 and 10. The first was an A-->G transition at nucleotide position 2168, resulting in a predicted His-->Arg substitution at position 723 (H723R), whereas the second was a C-->T transition at nucleotide position 1229, resulting in a predicted Thr-->Met substitution at position 410 (T410M). Both mutations are situated in the extracellular domain close to the C terminal. It thus appears that PDS mutations can lead not only to classic Pendred syndrome, but also to large vestibular aqueduct syndrome.A recent report demonstrated the presence of a mutation in the Pendred syndrome gene (PDS) of patients with large vestibular aqueducts but without goitre. We studied PDS mutations in members of four Japanese families, among which five affected members showed bilateral enlarged vestibular aqueducts. All affected members exhibited moderate to severe bilateral fluctuating sensorineural hearing loss and the absence of goitre. Three members also suffered from recurrent episodic vertiginous spells. Analysis of PDS

Mitochondrial DNA Mutation at Nucleotide 1555 in a Patient with Bilateral Sensorineural Hearing Loss of Unknown Etiology

A mitochondrial DNA mutation at nucleotide 1555 in the ribosomal RNA gene was recently reported as a cause of maternally inherited non-syndromic sensorineural deafness. We assumed that the 1555 mutation is also associated with sporadic non-syndromic deafness and screened for the mutation in seven randomly selected sporadic cases with bilateral sensorineural hearing loss of unknown etiology. The mutation was found in one patient, who first noticed hearing loss when she was in her early teens with subsequent gradual progression. The results suggest that the 1555 mutation may contribute to the etiology of idiopathic bilateral sensorineural hearing loss in some cases.

A new mutation in the POU3F4 gene in a Japanese family with X-linked mixed deafness (DFN3)

Objective: The molecular defect in patients with X‐linked mixed deafness showing a perilymphatic gusher at stapedectomy (DFN3) has been attributed to mutations in the POU3F4 gene. This study aimed to clarify an allelic variant of this gene. Study Design: This was a genetic study of a single Japanese family with DFN3. Methods: Products of a polymerase chain reaction (PCR) were subjected to single‐strand conformation polymorphism (SSCP) analysis. Direct sequencing of PCR products from patients and carriers showing SSCP variants was performed using the fluorescent dideoxy termination method and a sequencer. Results: Sequencing of the PCR product revealed a 6‐base deletion (TTCAAA) at nucleotides 601 to 606, resulting in a two‐amino‐acid deletion in the POU3F4 protein, (phenylalanine and lysine at amino acid residues 201 and 202). The deletion was adjacent to the site of a nonsense mutation previously described. Conclusion: Microdeletions at a previously undescribed location account for some clinically important POU3F4 mutations. Laryngoscope, 108:1544–1547, 1998

Hereditary Sensorineural Hearing Loss of Unknown Cause Involving Mitochondrial DNA 1555 Mutation

We report on a family with maternally inherited sensorineural hearing loss, in which no history of aminoglycoside injection and no other specific etiology could be identified in any member. A 1555 A-to-G mutation of mitochondrial DNA was found in all members demonstrating hearing loss. The hearing in the propositus and his sister was severely impaired at a younger age than that in the mother. This case suggests that the 1555 point mutation of mitochondrial DNA has potential to promote inherited nonsyndromic hearing loss without any known etiology.

Audiologic features of hearing loss due to the 1,555 mutation of mitochondrial DNA

We proved a 1,555 mutation of mitochondrial DNA in one member of each of three families with familial streptomycin hearing loss, and report the pedigrees and audiologic features. DNA was extracted by the standard method. The 1,555 A to G mutation was identified in all three patients and confirmed by direct sequencing of the polymerase chain reaction products by a cycle sequencing method. On audiograms, the hearing loss was sensorineural, bilateral, and symmetric, showing a high-tone loss or a profound loss particularly in the high-tone range, and the “symmetry law” of Langenbeck was applicable. The superimposed audiograms of members of one family did not cross themselves, proving the applicability of the “never-cross principle of audiograms.”

Branchial cyst of the nasopharynx: resection via the endonasal approach.

We present a rare branchial cyst of the nasopharynx in a 57-year-old man. The cyst was located at the higher level between the roof and the left lateral band of the nasopharynx, and was removed by the endonasal approach following a preparatory septoplasty. While several cases of nasopharyngeal cysts have previously been reported, this appears to be the first case of the resection of such a cyst via the endonasal approach, and is a useful, and potentially less injurious, alternative to the transpalatal approach.