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Biomedical subjects

Tatsuo Matsunaga

Publications and source records attributed to Tatsuo Matsunaga.

12 recordsLinked to original sources
PubMed2025

ClinGen recuration of hearing loss-associated genes demonstrates significant changes in gene-disease validity over time.

PURPOSE: The Clinical Genome Resource (ClinGen) Hearing Loss Gene Curation Expert Panel was assembled in 2016 and has since curated 174 gene-disease relationships (GDRs) using ClinGen's semiquantitative framework. ClinGen mandates the timely recuration of all GDRs classified as Disputed, Limited, Moderate, and Strong every 2 to 3 years. METHODS: Thirty-five GDRs met the criteria for recuration within 2 years of original curation. Previous evidence was reevaluated using the latest curation guidelines, and a comprehensive literature review was performed to obtain new evidence. Recurations were approved by the Gene Curation Expert Panel and published on the ClinGen website (www.clinicalgenome.org). RESULTS: Eight of 35 GDRs (22%) changed their classification. Two Moderate and 5 Strong GDRs were upgraded to Definitive because of new case evidence. One Strong was subsumed under another Definitive GDR after evaluation of the lumping/splitting of disease entities. Twenty-seven of 35 patients remained unchanged, with little to no new evidence reported. CONCLUSION: Genes classified as Moderate and Strong were likely to build evidence and change their classification over time, whereas Limited were unlikely to gain evidence. These findings highlight the critical role of recuration in ensuring that genetic tests and research studies incorporate the most recent evidence into their efforts.

Humans↗
PubMed2005

Clinical course of hearing and language development in GJB2 and non-GJB2 deafness following habilitation with hearing aids.

Mutations in the GJB2 gene (connexin 26) are the most common cause of nonsyndromic autosomal recessive sensorineural hearing loss. Genetic testing of GJB2 may offer opportunities to predict the features of hearing loss and prognostication of speech-language development in children with hearing loss. The present study assessed the clinical features of hearing and some aspects of language development in congenital deafness due either to GJB2 mutations or to other factors in Japanese patients who had been habilitated with hearing aids. Thirty-five unrelated subjects with nonsyndromic, congenital, bilateral sensorineural hearing loss were enrolled in the study. Among them, 16 had biallelic GJB2 mutations related to hearing loss and 17 lacked such mutations. As has been reported in populations of European ancestry, the present Japanese subjects with GJB2 mutations had a relatively high incidence of the flat pattern audiogram and nonprogressive pure tone thresholds compared with subjects without GJB2 mutations. Subjects with GJB2 mutations and those without GJB2 mutations both showed a similar tendency in speech perception, some aspects of language development, and communication methods. In both groups, development of reading ability tended to be normal, but vocabulary development tended to be delayed. The present results establish the basis for future studies to aid in the evaluation and follow-up of patients with congenital hearing loss associated with GJB2 mutations who are habilitated with hearing aids.

Adolescent↗
PubMed2005

Permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by degeneration of the lateral wall of the cochlea.

Mitochondrial dysfunction in the cochlea is thought to be an important cause of sensorineural hearing loss. Recently, we have established a novel rat model with acute hearing impairment caused by exposure to the mitochondrial toxin 3-nitropropionic acid (3-NP) to analyze the mechanism of cochlear mitochondrial dysfunction. Both permanent and temporary threshold shifts were observed in this model depending on the amount of 3-NP used to induce hearing impairment. In this study, we demonstrate cochlear morphological changes in the permanent threshold shift model. Marked degeneration was detected in type 2 fibrocytes in the spiral prominence, type 4 fibrocytes in the spiral ligament, marginal cells and intermediate cells in the stria vascularis 3 h after 3-NP administration; these changes were progressive for at least 14 days. Less prominent degeneration was detected in type 1 and type 3 fibrocytes in the spiral ligament. These results indicate that permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by cellular degeneration in the lateral wall of the cochlea, and suggest that therapy of cochlear hearing loss due to acute energy failure may be achieved through protection and regeneration of the cochlear lateral wall.

Acute Disease↗
PubMed2005

Clinical features of patients with GJB2 (connexin 26) mutations: severity of hearing loss is correlated with genotypes and protein expression patterns.

Mutations in the GJB2 (connexin 26, Cx26) gene are the major cause of nonsyndromic hearing impairment in many populations. Genetic testing offers opportunities to determine the cause of deafness and predict the course of hearing, enabling the prognostication of language development. In the current study, we compared severity of hearing impairment in 60 patients associated with biallelic GJB2 mutations and assessed the correlation of genotypes and phenotypes. Within a spectrum of GJB2 mutations found in the Japanese population, the phenotype of the most prevalent mutation, 235delC, was found to show more severe hearing impairment than that of V37I, which is the second most frequent mutation. The results of the present study, taken together with phenotypes caused by other types of mutations, support the general rule that phenotypes caused by the truncating GJB2 mutations are more severe than those caused by missense mutations. The present in vitro study further confirmed that differences in phenotypes could be explained by the protein expression pattern.

Adolescent↗
PubMed2005

Audiological features and mitochondrial DNA sequence in a large family carrying mitochondrial A1555G mutation without use of aminoglycoside.

To elucidate the pathophysiological and genetic mechanisms of hearing loss associated with the homoplasmic mitochondrial A1555G mutation in the absence of aminoglycoside exposure, we conducted audiological and genetic analyses on 67 maternally related members of a large Japanese family carrying this mutation. A consistent pattern was evident in the audiograms, with features of sensory presbycusis, cochlear origin at all levels of hearing loss, and a high degree of vulnerability of outer hair cells. That the degree of hearing loss was similar in affected subjects within the same sibling group but differed between sibling groups suggests the involvement of nuclear modifier genes. Total mitochondrial DNA sequences were completely identical among subjects with various levels of hearing loss, and lacked additional pathogenic mutations. For the diagnosis of sensorineural hearing loss, the mitochondrial A1555G mutation should be considered when these features are present even in the absence of aminoglycoside exposure.

Adolescent↗
PubMed2004

A novel animal model of acute cochlear mitochondrial dysfunction.

Acute mitochondrial dysfunction in the cochlea is likely to result in hearing loss as a consequence of local energy shortage, similar to ischemia- or noise-induced hearing loss. To establish an animal model of acute cochlear mitochondrial dysfunction, we applied a mitochondrial toxin, 3-nitropropionic acid (3-NP) in the rat cochlea. Rats treated with 500mM 3-NP exhibited permanent threshold shifts in acoustic brainstem response while the same volume of 300mM 3-NP caused temporary threshold shifts. Histological examination in the permanent threshold shift model revealed severe degeneration of fibrocytes within spiral ligament and spiral limbus, indicating these cells are vulnerable to acute mitochondrial dysfunction. This model represents a novel tool for investigating the pathophysiology of acute cochlear mitochondrial dysfunction.

Animals↗
PubMed2004

Deafness due to A1555G mitochondrial mutation without use of aminoglycoside.

OBJECTIVES/HYPOTHESIS: The objective was to clarify the characteristics of deafness associated with the A1555G mutation within mitochondrial 12S ribosomal RNA gene in the absence of aminoglycoside exposure. STUDY DESIGN: Clinical and genetic studies in family members with the A1555G mitochondrial mutation were performed. METHODS: The subjects were 123 maternally related members of a large Japanese family with the A1555G mutation. All subjects had no previous history of exposure to aminoglycosides. Hearing disability and handicap, tinnitus, and medical histories were analyzed by interviews in all of the subjects, genetic testing was performed in 41 subjects, and pure-tone audiometry was conducted in 26 subjects with hearing disability and handicap. RESULTS: The A1555G mutation was detected in a homoplasmic form (meaning that all the mitochondrial DNA carries the mutation) in all 41 subjects who were screened. The risk for developing postlingual hearing loss was likely to be much higher in the present subjects than in the general population. Both the severity and age at onset of the phenotype were similar in affected subjects within the same sibling group. Pure-tone averages were significantly worse in subjects who developed hearing loss before age 10 years than in those who developed hearing loss later. CONCLUSION: The present study demonstrated that the prevalence of deafness in individuals with the A1555G mitochondrial mutation was likely to be high even in the absence of aminoglycoside exposure and clearly showed the association of severe to profound hearing loss with the onset of hearing loss before age 10 years.

Adolescent↗
PubMed2003

Familial lateral semicircular canal malformation with external and middle ear abnormalities.

We report a family with inner ear lateral semicircular canal (LSC) malformation and external and middle ear abnormalities. The family had no history of known syndromes or toxic exposures. Distinct phenotypic manifestations were found in three family members. A young girl exhibited bilateral LSC malformation with a right-sided preauricular tag, a mildly deformed auricle, a stenotic external auditory canal, and a constricted middle ear cavity. She had moderate conductive hearing loss in the right ear but normal hearing in the left ear. Her younger brother exhibited right-sided LSC malformation, microtia, external auditory canal atresia, a malformed middle ear cavity, and abnormal auditory ossicles. He had severe mixed hearing loss in his right ear. Their mother exhibited left-sided LSC malformation without external and middle ear abnormalities, and the hearing was normal in her left ear. None of the three cases had vestibular symptoms, and their results of balance tests were appropriate for the corresponding ages. In contrast, significantly decreased LSC function was revealed by caloric tests in an ear with LSC malformation. Previously, LSC malformation may have been underdiagnosed in patients presenting with external and middle ear abnormalities and their relatives, since this malformation is frequently associated with normal hearing and balance or conductive hearing loss only. To our knowledge, this condition has not been described previously. This condition supports a genetic basis for the combination of LSC malformation and external and middle ear abnormalities and may represent an autosomal dominant condition with variable expressivity.

Adult↗
PubMed2002

Identification of 605ins46, a novel GJB2 mutation in a Japanese family.

Connexin 26 gene (GJB2) mutations are known to be responsible for a significant portion (30-80%) of autosomal recessive congenital severe to profound deafness. More than 60 recessive mutations in GJB2 have been reported and most consist of point mutations of a nucleotide. We report here a novel insertional GJB2 mutation consisting of a long repetitive nucleotide sequence. As compound heterozygotes of this mutation with 235delC express sensorineural hearing loss of variable severity, further analysis of the phenotype-genotype relationship is required.

Child↗