耳鼻咽喉科・頭頸部外科89巻1号

2017年01月発行

特集 めまい診療のNew Trend 《最新のめまい診断》

遺伝子検査とめまい診断

著者： 野口佳裕¹

所属機関： ¹信州大学医学部人工聴覚器学講座

ページ範囲：P.30 - P.34

POINT

●片頭痛関連めまい（前庭性片頭痛），周期性失調症，家族性両側前庭機能低下症に関する遺伝学的研究が進行中である。

●めまい・平衡障害を伴う代表的な遺伝性難聴として，DFNA9，DFNB4/Pendred症候群，Usher症候群が挙げられる。

●常染色体優性遺伝性メニエール病の原因候補遺伝子としてPRKCBが同定されている。

参考文献

1）野口佳裕：メニエール病と遺伝子．Equilibrium Res 71：247-251，2012

2）五島史行・他：「片頭痛関連めまい」補遺：Vestibular migraine：の国際頭痛分類第三版β（ICHD-III beta）への収載．Equilibrium Res 72：504，2013

3）Lee H, et al：Phenotypic and genetic analysis of a large family with migraine-associated vertigo. Headache 48：1460-1467, 2008

4）Bahmad F Jr, et al：Locus for familial migrainous vertigo disease maps to chromosome 5q35. Ann Otol Rhinol Laryngol 118：670-676, 2009

5）von Brevern, et al：Migrainous vertigo：mutation analysis of the candidate genes CACNA1A, ATP1A2, SCN1A, and CACNB4. Headache 46：1136-41, 2006

6）Jen JC, et al：Familial episodic ataxia：a model for migrainous vertigo. Ann N Y Acad Sci 1164：252-256, 2009

7）Gazquez I, et al：Genetics of recurrent vertigo and vestibular disorders. Curr Genomics 12：443-450, 2011

8）Jen JC, et al：Suggestive linkage to chromosome 6q in families with bilateral vestibulopathy. Neurology 63：2376-2379, 2004

9）Tsukada K, et al：Detailed hearing and vestibular profiles in the patients with COCH mutations. Ann Otol Rhinol Laryngol 124 Suppl 1：100S-110S, 2015

10）Bae SH, et al：Identification of pathogenic mechanisms of COCH mutations, abolished cochlin secretion, and intracellular aggregate formation：genotype-phenotype correlations in DFNA9 deafness and vestibular disorder. Hum Mutat 35：1506-1513, 2014

11）Usami S, et al：Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochlea-vestibular dysfunction, but not of Meniere's disease. Eur J Hum Genet 11：744-748, 2003

12）Kim HJ, et al：SNP linkage analysis and whole exome sequencing identify a novel POU4F3 mutation in autosomal dominant late-onset nonsyndromic hearing loss（DFNA15）. PLos One 8：e79063, 2013

13）van Drunen FJ, et al：Vestibular impairment in a Dutch DFNA15 family with an L289F mutation in POU4F3. Audiol Neurootol 14：303-307, 2009

14）Seco CZ, et al：Progressive hearing loss and vestibular dysfunction caused by a homozygous nonsense mutation in CLIC5. Eur J Hum Genet 23：189-194, 2015

15）Noguchi Y, et al：A nationwide study on enlargement of the vestibular aqueduct in Japan. Auris Nasus Larynx 43：495-500, 2016

16）Pryor SP, et al：SLC26A4/PDS genotype-phenotype correlation in hearing loss with enlargement of the vestibular aqueduct（EVA）：evidence that Pendred syndrome and non-syndromic EVA are distinct clinical and genetic entities. J Med Genet 42：159-165, 2005

17）Miyagawa M, et al：Mutation spectrum and genotype-phenotype correlation of hearing loss patients caused by SLC26A4 mutations in the Japanese：a large cohort study. J Hum Genet 59：262-268, 2014

18）Suzuki H, et al：Clinical characteristic and genotype-phenotype correlation of hearing loss patients with SLC26A4 mutations. Acta Otolaryngol 127：1292-1297, 2007

19）野口佳裕・他：前庭水管拡大症を伴うSLC26A4，ATP6V1B1，SIX1変異例の聴平衡覚所見の検討．Equilibrium Res 72：97-106，2013．

20）Yashima T, et al：Novel ATP6V1B1 mutations in distal renal tubular acidosis and hearing loss. Acta Otolaryngol 130：1002-1008, 2010

21）Ito T, et al：SIX1 mutation associated with enlargement of the vestibular aqueduct in a patient with Branchio-Oto syndrome. Laryngoscope 116：796-799, 2006.

22）Noguchi Y, et al：Audiovestibular findings in a branchio-oto syndrome patient with a SIX1 mutation. Acta Otolaryngol 131：413-418, 2011

23）Ito T, et al：Slc26a4-insufficiency causes fluctuating hearing loss and stria vascularis. Neurobiol Dis 66：53-65, 2014

24）岩崎 聡・他：Usher症候群の臨床タイプ分類の問題点．日耳鼻115：894-901，2012

25）吉村豪兼・他：Usher症候群タイプ1の原因遺伝子と前庭機能評価についての検討．Equilibrium Res 72：467-471，2013

26）Yoshimura H, et al：Identification of a novel CLRN1 gene mutation in Usher syndrome type 3：two case reports. Ann Otol Rhinol Laryngol 124 Suppl 1：94S-99S, 2015

27）Gabriková D, et al：Familiar Meniere's disease restricted to 1.48 Mb on chromosome 12p12.3 by allelic and haplotype association. J Hum Genet 55：834-837, 2010

28）Martin-Sierra C, et al：A novel missense variant in PRKCB segregates low-frequency hearing loss in an autosomal dominant family with Meniere's disease. Hum Mol Genet 2016 Jun 21. pii：ddw183（印刷中）