難聴の遺伝子解析と臨床応用に関する研究

• 研究課題/領域番号: 12307036
• 研究種目: 基盤研究(A)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 耳鼻咽喉科学
• 研究機関: 信州大学
• 研究代表者: 宇佐美 真一 信州大学, 医学部, 教授 (10184996)
• 研究分担者: 松原 篤 弘前大学, 医学部附属病院, 講師 (10260407) ; 甲田 英子 信州大学, 医学部付属病院, 助手 (20322133) ; 佐藤 圭司 信州大学, 医学部, 助手 (90293480)
• 研究期間 (年度): 2000 – 2003
• 研究課題ステータス: 完了 (2003年度)
• 配分額: 43,500千円 (直接経費: 37,200千円、間接経費: 6,300千円); 2003年度: 9,100千円 (直接経費: 7,000千円、間接経費: 2,100千円); 2002年度: 9,100千円 (直接経費: 7,000千円、間接経費: 2,100千円); 2001年度: 9,100千円 (直接経費: 7,000千円、間接経費: 2,100千円); 2000年度: 16,200千円 (直接経費: 16,200千円)
• キーワード: 難聴 / 遺伝子 / コネキシン26遺伝子 / PDS遺伝子 / インベーダー法 / 遺伝カウンセリング / GJB2 / PDS / KCNQ4 / COCH / KCNQ4遺伝子 / COCH遺伝子 / CX26遺伝子 / ミトコンドリア遺伝子 / DNAチップ / Cx26遺伝子

研究概要

今回の研究で日本人難聴患者の遺伝子解析を行った結果、PDS遺伝子、コネキシン26遺伝子、ミトコンドリア遺伝子、EYA1遺伝子、KCNQ4遺伝子、COCH遺伝子、TECTA遺伝子などの難聴原因遺伝子が日本人難聴患者に深く関与していることが明らかになった。また高頻度で見出される難聴遺伝子として知られているコネキシン26遺伝子変異およびPDS遺伝子に関して、欧米の報告と比較検討したところ日本人難聴患者に見出される遺伝子変異の種類は全く異なることが明らかになった。これらの日本人家系を用いた遺伝子解析のデータベースは、今後、難聴患者の診断、治療、カウンセリングを行なっていく上で重要な基礎データとなると思われる。また今回、共同研究により内耳に特異的に高発現する遺伝子が明らかとなり、日本人難聴家系から新たな難聴の原因遺伝子としてCOL9A3,ATP1A2の各遺伝子が発見された。種々の難聴の原因遺伝子が難聴をおこすメカニズムに関しては、日本人難聴家系に見出されたコネキシン26遺伝子変異を細胞に導入し細胞内局在を観察し臨床型(難聴の程度)と比較検討した。その結果、細胞膜に蛋白が発現しない変異(235de1C)は発現する変異(V37I)に比較し難聴が一般的に高度であることが明らかとなった。したがって遺伝子検索によってある程度難聴の程度が推測できる可能性が示唆された。今後これらの成果を臨床にフィードバックするには簡便な簡便なスクリーニング法の開発が必要不可欠である。今回の研究では多数の遺伝子変異を同時に検出可能なインベーダー法を用いたスクリーニング法の開発を行った。遺伝子診断に伴う種々の倫理的問題に関しては信州大学附属病院遺伝子診療部と共同研究を行い、各難聴遺伝子ごとに遺伝カウンセリングの重要点をリストアップした。

研究成果

• [文献書誌] Abe S: "Identification of CRYM as a candidate responsible for nonsyndromic deafness, through cDNA microarray analysis of human cochlear and vestibular tissues"Am J Hum Genet. 72(1). 73-82 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Abe S: "Construction and characterization of a vestibular-specific cDNA library using T7-based RNA amplification"J Hum Genet. 48(3). 142-149 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Ohtsuka A: "GJB2 deafness gene shows a specific spectrum of mutations in Japan, including a frequent founder mutation"Hum Genet. 112(4). 329-333 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Park HJ: "Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians : global implications for the epidemiology of deafness"J Med Genet. 40(4). 242-248 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Usami S: "Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere's disease"Eur J Hum Genet. 11(10). 744-748 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Abe S: "Mutations in the gene encoding KIAA1199 protein, an inner-ear protein expressed in Deiters' cells and the fibrocytes, as the cause of nonsyndromic hearing loss"J Hum Genet. 48(11). 564-570 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Tsukamoto K: "Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct : a unique spectrum of mutations in Japanese"Eur J Hum Genet. 11(12). 916-922 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Ishinaga H: "Pendred's syndrome with goiter and enlarged vestibular aqueducts diagnosed by PDS gene mutation"Head Neck. 24(7). 710-713 (2002)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Van Camp G: "A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment"Hum Mutat. 20(1). 15-19 (2002)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Yuge I: "Identification of 605ins46, a novel GJB2 mutation in a Japanese family"Auris Nasus Larynx. 29(4). 379-382 (2002)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Usami SI: "Molecular diagnosis of deafness : impact of gene identification"Audiol Neurootol. 7(3). 185-190 (2002)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Sugata A: "High-throughput screening for GJB2 mutations-its clinical application to genetic testing in prelingual deafness screening for GJB2 mutations"Auris Nasus Larynx. 29(3). 231-239 (2002)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Iwasaki S: "Association of Clinical Features With Mutation of TECTA in a Family With Autosomal Dominant Hearing Loss"Otolaryngol Head Neck Surg. 128(8). 913-917 (2002)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] De Leenheer EM: "DFNA2/KCNQ4 and its manifestations"Adv Otorhinolaryngol. 61. 41-46 (2002)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Namba A: "Genetic features of hearing loss associated with ear anomalies : PDS and EYA1 mutation analysis"J Hum Genet. 46(9). 518-521 (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Abe S: "Connexin 26 gene (GJB2) mutation modulates the severity of hearing loss associated with the 1555A-->G mitochondrial mutation"Am J Med Genet. 103(4). 334-338 (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Fukuda S: "A family affected by branchio-oto syndrome with EYA1 mutations"Auris Nasus Larynx. 28(Suppl). S7-S11 (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Tono T: "Different clinical characteristics of aminoglycoside-induced profound deafness with and without the 1555 A-->G mitochondrial mutation"ORL J Otorhinolaryngol Relat Spec. 63(1). 25-30 (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Masuda M: "Connexin 26 distribution in gap junctions between melanocytes in the human vestibular dark cell area"Anat Rec. 262(2). 137-146 (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Iwasaki S: "Long-term audiological feature in Pendred syndrome caused by PDS mutation"Arch Otolaryngol Head Neck Surg. 127(6). 705-708 (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Akita I: "Clinical and genetic features of nonsyndromic autosomal dominant sensorineural hearing loss : KCNQ4 is a gene responsible in Japanese"J Hum Genet. 46(7). 355-361 (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Weston MD: "Genomic Structure and Identification of Novel Mutations in Usherin, the Gene Responsible for Usher Syndrome Type IIa"Am J Hum Genet. 66(4). 1199-1210 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Usami S: "Glutamate neurotransmission in the mammalian inner ear"in Handbook of Chemical Neuroanatomy. 18. 255-271 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Usami S: "Sensorineural hearing loss associated with the mitochondrial mutations"Adv Otorhinolaryngol. 56. 203-211 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Abe S: "Prevalent connexin 26 gene (GJB2) mutations in Japanese"J Med Genet. 37(1). 41-43 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Usami S: "Prevalence of mitochondrial gene mutations among hearing impaired patients"J Med Genet. 37(1). 38-40 (2000)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] 宇佐美 真一: "遺伝カウンセリングマニュアル(福嶋義光編):耳鼻科疾患"本郷 允彦. 1-360 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Abe S: "identification of CRYM as a candidate responsible for nonsyndromic deafness, through cDNA microarray analysis of human cochlear and vestibular tissues"Am J Hum Genet. 72(1). 73-82 (2003)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Abe S: "Construction and characterization of a vestibular-specific cDNA library using T7-based RNA amplification"J Hum Genet. 48(3). 142-149 (2003)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Ohtsuka A: "GJB2 deafness gene shows a specific spectrum of mutations in Japan, including a frequent founder mutation"Hum Genet. 112(4). 329-333 (2003)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Park HJ: "Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians : global implications for the epidemiology of deafness"J Med Genet. 40(4). 242-248 (2003)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Usami S: "mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere's disease"Eur J Hum Genet. 11(10). 744-748 (2003)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Abe S: "Mutations in the gene encoding KIAA1199 protein, an inner-ear protein expressed in Deiters' cells and the fibrocytes, as the cause of nonsyndromic hearing loss"J Hum Genet. 48(11). 564-570 (2003)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Tsukamoto K: "Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct : a unique spectrum of mutations in Japanese"Eur J Hum Genet. 11(12). 916-922 (2003)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Ishinaga H: "Pendred's syndrome with goiter and enlarged vestibular aqueducts diagnosed by PDS gene mutation"Head Neck. 24(7). 710-713 (2002)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Van Camp G: "A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment"Hum Mutat. 20(1). 15-19 (2002)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Yuge I: "Identification of 605ins46, a novel GJB2 mutation in a Japanese family"Auris Nasus Larynx. 29(4). 379-382 (2002)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Usami SI: "Molecular diagnosis of deafness : impact of gene identification"Audiol Neurootol. 7(3). 185-190 (2002)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Sugata A: "High-throughput screening for GJB2 mutations-its clinical application to genetic testing in prelingual deafness screening for GJB2 mutations"Auris Nasus Larynx. 29(3). 231-239 (2002)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Iwasaki S: "Association of Clinical Features With Mutation of TECTA in a Family With Autosomal Dominant Hearing Loss"Arch Otolaryngol Head Neck Surg. 128(8). 913-917 (2002)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] De Leenheer EM: "DFNA2/KCNQ4 and its manifestations"Adv Otorhinolaryngol. 61. 41-46 (2002)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Namba A: "Genetic features of hearing loss associated with ear anomalies : PDS and EYA1 mutation analysis"J Hum Genet. 46(9). 518-521 (2001)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Abe S: "Connexin 26 gene (GJB2) mutation modulates the severity of hearing loss associated with the 1555A-->G mitochondrial mutation"Am J Med Genet. 103(4). 334-338 (2001)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Fukuda S: "A family affected by branchio-oto syndrome with EYA1 mutations"Auris Nasus Larynx. 28(Suppl). S7-S11 (2001)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Tono T: "Different clinical characteristics of aminoglycoside-induced profound deafness with and without the 1555 A-->G mitochondrial mutation"ORL J Otorhinolaryngol Relat Spec. 63(1). 25-30 (2001)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Masuda M: "Connexin 26 distribution in gap junctions between melanocytes in the human vestibular dark cell area"Anat Rec. 262(2). 137-146 (2001)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Iwasaki S: "Long-term audiological feature in Pendred syndrome caused by PDS mutation"Arch Otolaryngol Head Neck Surg. 127(6). 705-708 (2001)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Akita J: "Clinical and genetic features of nonsyndromic autosomal dominant sensorineural hearing loss : KCNQ4 is a gene responsible in Japanese"J Hum Genet. 47(7). 355-361 (2001)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Weston MD: "Genomic Structure and Identification of Novel Mutations in Usherin, the Gene Responsible for Usher Syndrome Type IIa"Am J Hum Genet. 66(4). 1199-1210 (2000)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Usami S: "Glutamate neurotransmission in the mammalian inner ear"Handbook of Chemical Neuroanatomy (eds. Otterson OP & Storm-Mathisen J). Vol.18. 255-271 (2000)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Usami S: "Sensorineural hearing loss associated with the mitochondrial mutations"Adv Otorhinolaryngol. 56. 203-211 (2000)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Abe S: "Prevalent connexin 26 gene (GJB2) mutations in Japanese"J Med Genet. 37(1). 41-43 (2000)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Usami S: "Prevalence of mitochondrial gene mutations among hearing impaired patients"j Med Genet. 37(1). 38-40 (2000)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Abe S: "Construction and characterization of a vestibular-specific cDNA library using T7-based RNA amplification"J Hum Genet. 48・3. 142-149 (2003)
• [文献書誌] Park HJ: "Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians : global implications for the epidemiology of deafness"J Med Genet. 40・4. 242-248 (2003)
• [文献書誌] Usami S: "Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere's disease"Eur J Hum Genet. 11・10. 744-748 (2003)
• [文献書誌] Abe S: "Mutations in the gene encoding KIAA1199 protein, an inner-ear protein expressed in Deiters' cells and the fibrocytes, as the cause of nonsyndromic hearing loss"J Hum Genet. 48・11. 564-570 (2003)
• [文献書誌] Tsukamoto K: "Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct : a unique spectrum of mutations in Japanese"Eur J Hum Gene. 11・12. 916-922 (2003)
• [文献書誌] 宇佐美 真一: "遺伝カウンセリングマニュアル(福嶋義光編) : 耳鼻科疾患"本郷 允彦. 1,360 (2003)
• [文献書誌] Ohtsuka A, Yuge I, Kimura S, Namba A, Abe S, Van Laer L, Van Camp G, Usami S.: "GJB2 deafness gene shows a specific spectrum of mutations in Japan, including a frequent founder mutation"Hum Genet. 112・4. 329-333 (2003)
• [文献書誌] Abe S, Katagiri T, Saito-Hisaminato A, Usami S, Inoue Y, Tsunoda T, Nakamura Y.: "Identification of CRYM as a candidate responsible for nonsyndromic deafness, through cDNA microarray analysis of human cochlear and vestibular tissues"Am J Hum Genet. 72・1. 73-82 (2003)
• [文献書誌] Usami SI, Koda E, Tsukamoto K, Otsuka A, Yuge I, Asamura K, Abe S, Akita J, Namba A.: "Molecular diagnosis of deafness : impact of gene identification"Audiol Neurootol. 7・3. 185-190 (2002)
• [文献書誌] Iwasaki S, Harada D, Usami S, Nagura M, Takeshita T, Hoshino T.: "Association of Clinical Features With Mutation of TECTA in a Family With Autosomal Dominant Hearing Loss"Arch Otolaryngol Head Neck Surg. 128・8. 913-917 (2002)
• [文献書誌] De Leenheer EM, Ensink RJ, Kunst HP, Marres HA, Talebizadeh Z, Declau F, Smith SD, Usami S, Van de Heyning PH, Van Camp G, Huygen PL, Cremers CW.: "DFNA2/KCNQ4 and its manifestations"Adv Otorhinolaryngol. 61. 41-46 (2002)
• [文献書誌] Yuge I, Ohtsuka A, Matsunaga T, Usami S.: "Identification of 605ins46, a novel GJB2 mutation in a Japanese family"Auris Nasus Larynx. 29・4. 379-382 (2002)
• [文献書誌] Iwasaki S, Harada D, Usami S, Nagura M, Takeshita T, Hoshino T.: "Association of Clinical Features with Mutation of TECTA in an Autosomal Dominant Hearing Loss Family"Arch Otolaryngol Head Neck Surg 2002. (in press). (2002)
• [文献書誌] Usami S, Koda E, Tsukamoto K, Otsuka A, Yuge I, Asamura K.: "Molecular diagnosisi of deafness-impact of gene identification"Audiology & Neurootology 2002. (in press). (2002)
• [文献書誌] Ishinaga H, Shimizu T, Yuta A, Usami S, Tsukamoto K, Majima Y.: "endred's syndrome with goiter and enlarged vestibular aqueducts diagnosed by PDS gene mutation"Head and Neck 2002. (in press). (2002)
• [文献書誌] Van Camp G, Coucke PJ, Akita J, Fransen E, Abe S.: "Leenheer EMRD, Huygen PLM, Cremers CWRJ, Usami S. A mutational hot spot in the KCNQ4 gene, responsible for autosomal dominant hearing impairment"Human Mutation 2002. (in press). (2002)
• [文献書誌] Akita J, Abe S, Shinkawa H, Kimberling WJ, Usami S: "Clinical and genetic features of non-syndromic autosomal dominant sensorineural hearing loss : KCNQ4 is a responsible gene in Japanese"J Hum Genet. 46. 355-361 (2001)
• [文献書誌] Iwasaki S, Usami S, Abe S, Isoda H, Watanabe T, Hoshino T.: "Long-term audiological feature in Pendred syndrome caused by PDS mutation"Arch Otolaryngol Head Neck Surg. 127(6). 705-708 (2001)
• [文献書誌] Masuda M, Usami S, Yamazaki K, Takumi Y, Shinkawa H, Kurashima K, Kunihiro T, Kanzaki J.: "Connexin 26 distribution in gap junctions between melanocytes in the human vestibular dark cell area"Anat Rec. 262(2). 137-146 (2001)
• [文献書誌] Takumi Y, Matsubara A, Tsuchida S, Ottersen OP, Shinkawa H, Usami S.: "Takumi Y, Matsubara A, Tsuchida S, Ottersen OP, Shinkawa H, Usami S."Neuroreport. 12(7). 1513-1516 (2001)
• [文献書誌] Tono T, Kiyomizu K, Matsuda K, Komune S, Usami S, Abe S, Shinkawa H.: "Different Clinical Characteristics of Aminoglycoside-Induced Profound Deafness with and without the 1555A->G Mitochondrial Mutation"ORL. 63. 25-30 (2001)
• [文献書誌] Namba A, Abe S, Shinkawa H, Kimberling WJ, Usami SI.: "enetic features of hearing loss associated with ear anomalies : PDS and EYA1 mutation analysis"J Hum Genet. 46(9). 518-521 (2001)
• [文献書誌] Abe S, Kelley PM, Kinberling WJ, Usami Si S: "Connexin 26 gene(GJB2)mutation modulates the severity of hearing loss associated with the 1555A-->G mitochondrial mutation"Am J Med Genet. 103(4). 334-338 (2001)
• [文献書誌] Fukuda S, Kuroda T, Chida E, Shimizu R, Usami S, Koda E, Abe S, Namba A, Kitamura K, Inuyama Y.: "A family affected by branchio-oto syndrome with EYA1 mutations"Auris Nasus Larynx. 28(Suppl). S7-S11 (2001)
• [文献書誌] Akita J,Abe S,Shinkawa H,Kimberling WJ,Usami S.: "Clinical and genetic features of non-syndromic autosomal dominant sensorineural hearing loss : KCNQ4 is a responsible gene in Japanese."J Hum Gent. (in press).
• [文献書誌] Namba A,Abe S,Shinkawa H,Kimberling WJ,Usami S.: "Genetic features of hearing loss associated with ear anomaly."J Hum Gent. (in press).
• [文献書誌] Tono T,Kiyomizu K,Matsuda K,Komune S,Usami S,Abe S,Shinkawa H.: "Different Clinical Characteristics of Aminoglycoside-Induced Profound Deafness with and without the 1555A->G Mitochondrial Mutation."ORL. 63. 25-30 (2001)
• [文献書誌] Weston MD,Eudy JD,Fujita S,Yao S,Usami S,Cremers C,Greenburg J,Ramesar R,Martini A,Moller C,Smith RJ,Sumegi J,Kimberling WJ.: "Genomic Structure and Identification of Novel Mutations in Usherin, the Gene Responsible for Usher Syndrome Type IIa."Am J Hum Genet. 66. 1199-1210 (2000)
• [文献書誌] Abe S,Usami S,Shinkawa H,Kelley PM,Kimberling WJ.: "Prevalent connexin 26 gene (GJB2) mutations in Japanese."J Med Genet. 37. 41-43 (2000)
• [文献書誌] Usami S,Abe S,Akita J,Namba A,Shinkawa H et al.: "Prevalence of mitochondrial gene mutations among hearing impaired patients."J Med Genet. 37. 38-40 (2000)
• [文献書誌] Usami S,Abe S,Akita J,Shinkawa H,Kimberling WJ.: "Sensorineural hearing loss associated with the mitochondrial mutations. In "Genetics in Otorhinolaryngology" Adv Otorhinolaryngol, Vol.56"Kitamura K & SteelKP/Karger. 9 (2000)