Identification of a novel truncation mutation of EYA4 in moderate degree hearing loss by targeted exome sequencing

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• 作者：Hyun Seok Choi ; Ah Reum Kim ; Shin Hye Kim…
• 关键词：EYA4 ; Hearing loss ; Targeted exome sequencing ; DFNA10
• 刊名：European Archives of Oto-Rhino-Laryngology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：273
• 期：5
• 页码：1123-1129
• 全文大小：1,090 KB
• 参考文献：1.Tekin M, Arnos KS, Pandya A (2001) Advances in hereditary deafness. Lancet 358(9287):1082–1090. doi:10.​1016/​S0140-6736(01)06186-4 CrossRef PubMed
  2.Morton NE (1991) Genetic epidemiology of hearing impairment. Ann N Y Acad Sci 630:16–31CrossRef PubMed
  3.Petit C (1996) Genes responsible for human hereditary deafness: symphony of a thousand. Nat Genet 14(4):385–391. doi:10.​1038/​ng1296-385 CrossRef PubMed
  4.Van Camp G, Smith RJ. Hereditary Hearing Loss Homepage. http://​hereditaryhearin​gloss.​org/​ . Accessed 1 May 2015
  5.Hildebrand MS, DeLuca AP, Taylor KR, Hoskinson DP, Hur IA, Tack D, McMordie SJ, Huygen PL, Casavant TL, Smith RJ (2009) A contemporary review of AudioGene audioprofiling: a machine-based candidate gene prediction tool for autosomal dominant nonsyndromic hearing loss. Laryngoscope 119(11):2211–2215. doi:10.​1002/​lary.​20664 CrossRef PubMed PubMedCentral
  6.Choi BY, Park G, Gim J, Kim AR, Kim BJ, Kim HS, Park JH, Park T, Oh SH, Han KH, Park WY (2013) Diagnostic application of targeted resequencing for familial nonsyndromic hearing loss. PLoS One 8(8):e68692. doi:10.​1371/​journal.​pone.​0068692 CrossRef PubMed PubMedCentral
  7.Hentze MW, Kulozik AE (1999) A perfect message: RNA surveillance and nonsense-mediated decay. Cell 96(3):307–310CrossRef PubMed
  8.Zimmerman JE, Bui QT, Steingrimsson E, Nagle DL, Fu W, Genin A, Spinner NB, Copeland NG, Jenkins NA, Bucan M, Bonini NM (1997) Cloning and characterization of two vertebrate homologs of the Drosophila eyes absent gene. Genome Res 7(2):128–141CrossRef PubMed
  9.Wayne S, Robertson NG, DeClau F, Chen N, Verhoeven K, Prasad S, Tranebjarg L, Morton CC, Ryan AF, Van Camp G, Smith RJ (2001) Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus. Hum Mol Genet 10(3):195–200CrossRef PubMed
  10.Pfister M, Toth T, Thiele H, Haack B, Blin N, Zenner HP, Sziklai I, Nurnberg P, Kupka S (2002) A 4-bp insertion in the eya-homologous region (eyaHR) of EYA4 causes hearing impairment in a Hungarian family linked to DFNA10. Mol Med 8(10):607–611PubMed PubMedCentral
  11.Schonberger J, Levy H, Grunig E, Sangwatanaroj S, Fatkin D, MacRae C, Stacker H, Halpin C, Eavey R, Philbin EF, Katus H, Seidman JG, Seidman CE (2000) Dilated cardiomyopathy and sensorineural hearing loss: a heritable syndrome that maps to 6q23-24. Circulation 101(15):1812–1818CrossRef PubMed
  12.Schonberger J, Wang L, Shin JT, Kim SD, Depreux FF, Zhu H, Zon L, Pizard A, Kim JB, Macrae CA, Mungall AJ, Seidman JG, Seidman CE (2005) Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss. Nat Genet 37(4):418–422. doi:10.​1038/​ng1527 CrossRef PubMed
  13.Makishima T, Madeo AC, Brewer CC, Zalewski CK, Butman JA, Sachdev V, Arai AE, Holbrook BM, Rosing DR, Griffith AJ (2007) Nonsyndromic hearing loss DFNA10 and a novel mutation of EYA4: evidence for correlation of normal cardiac phenotype with truncating mutations of the Eya domain. Am J Med Gen 143A(14):1592–1598. doi:10.​1002/​ajmg.​a.​31793 CrossRef
  14.Hildebrand MS, Coman D, Yang T, Gardner RJ, Rose E, Smith RJ, Bahlo M, Dahl HH (2007) A novel splice site mutation in EYA4 causes DFNA10 hearing loss. Am J Med Gen 143A(14):1599–1604. doi:10.​1002/​ajmg.​a.​31860 CrossRef
  15.Baek JI, Oh SK, Kim DB, Choi SY, Kim UK, Lee KY, Lee SH (2012) Targeted massive parallel sequencing: the effective detection of novel causative mutations associated with hearing loss in small families. Orphanet J Rare Dis 7:60. doi:10.​1186/​1750-1172-7-60 CrossRef PubMed PubMedCentral
  
• 作者单位：Hyun Seok Choi (1)
  Ah Reum Kim (2)
  Shin Hye Kim (2)
  Byung Yoon Choi (1) (3)
  
  1. Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, College of Medicine, Seoul National University, 300 Gumi-dong, Bundang-gu, Seongnam, Kyunggi, 463-707, Korea
  2. Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea
  3. Sensory Organ Research Institute, Seoul National University Medical Research Center, Seoul, Korea
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Otorhinolaryngology
  Neurosurgery
  Head and Neck Surgery
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1434-4726

文摘

The EYA4 gene encodes a 640-amino-acid protein that serves as a transcription factor. This protein contains a highly conserved Eya domain (eya-HR) and a variable domain (eya-VR). Mutations of this gene are known to cause postlingual and progressive sensorineural hearing loss, either as non-syndromic (DFNA10) or syndromic hearing loss, depending on the location of truncation of the mutant protein. Since our previous report, we have recruited 14 families segregating autosomal dominant moderate SNHL. A thorough medical history and physical examination including evaluation of heart problems ruled out any syndromic features in these families. Screening of EYA4 was performed by targeted exome sequencing of 134 known deafness genes (TES-134) from the probands. After basic filtering of the variants, we identified one proband who carried a novel truncation mutation, c.1194delT (p.Met401TrpfsX3) of EYA4, making the frequency of DFNA10 to be 7.14 % (1/14) in Koreans. The variant co-segregated perfectly with a slightly down-sloping, moderate degree of SNHL in the family (SH117), and was not detected in any of the 592 normal control chromosomes. This variant is likely to generate protein products that are truncated just downstream of the eya-VR domain. None of the three affected family members showed any syndromic features, including cardiac problems, which was compatible with a previous genotype–phenotype correlation. The identification of a novel EYA4 truncation mutation associated with DFNA10, rather than syndromic hearing loss, supports a previously reported genotype–phenotype correlation in this gene. Considering its detection rate, EYA4 mutations should be suspected in hereditary moderate hearing loss with a corresponding audiologic configuration, and a cardiac examination should be included in the initial evaluation.