MYO15A与遗传性耳聋
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摘要
MYO15A是常见的引起遗传性耳聋的基因。该基因突变导致常染色体隐性非综合征型耳聋(DFNB3),可能与伴有感音神经性耳聋的史密斯·马吉利综合征相关。小鼠模型研究发现,MYO15A突变引起内耳毛细胞静纤毛变短、特征性的阶梯状结构消失,听觉受损。目前已报道了200余个MYO15A突变位点,多样化的MYO15A突变听力表型以及MYO15A突变与听力表型之间的相关性。在MYO15A突变相关耳聋的治疗研究方面,对MYO15A突变的诱导多能干细胞进行基因校正与内耳毛细胞的诱导分化取得成功,在携带MYO15A突变的诱导型多能干细胞中已成功实现基因校正及毛细胞的诱导,证明MYO15A突变导致形态和功能缺陷可被有效逆转。本文总结了二十年来与MYO15A突变相关的遗传性耳聋研究。
MYO15 A is one of the common genes causing hereditary hearing loss. MYO15 variants can cause autosomal recessive nonsyndromic hearing loss(DFNB3) and is related with Smith-Magenis syndrome.Murine models studies show that MYO15 variants can lead to abnormal hearing function caused by short stereocilia and by loss of the normal staircase structure of stereocilia in hair cells. More than 200 MYO15 A variants have been reported to date. The phenotypes of MYO15 A variants are diversified and there may be a genotype-phenotype correlation. On genetic treatment of DFNB3, recent studies have demonstrated the feasibility of generating inner ear hair cells from human iPSCs and functional rescue of gene mutation-based deafness by genetic correction. The goal of this article is to provide a comprehensive review of MYO15 A variants related to hereditary hearing loss.
MYO15 A is one of the common genes causing hereditary hearing loss. MYO15 variants can cause autosomal recessive nonsyndromic hearing loss(DFNB3) and is related with Smith-Magenis syndrome.Murine models studies show that MYO15 variants can lead to abnormal hearing function caused by short stereocilia and by loss of the normal staircase structure of stereocilia in hair cells. More than 200 MYO15 A variants have been reported to date. The phenotypes of MYO15 A variants are diversified and there may be a genotype-phenotype correlation. On genetic treatment of DFNB3, recent studies have demonstrated the feasibility of generating inner ear hair cells from human iPSCs and functional rescue of gene mutation-based deafness by genetic correction. The goal of this article is to provide a comprehensive review of MYO15 A variants related to hereditary hearing loss.
引文
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7 Naz S,Imtiaz A,Mujtaba G,et al.Genetic causes of moderate to severe hearing loss point to modifiers[J].Clin Genet,2017,91(4):589-598.
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2 Wang A,Liang Y,Fridell RA,et al.Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3[J].Science,1998,280(5368):1447-1451.
3 Liang Y,Wang A,Belyantseva IA,et al.Characterization of the human and mouse unconventional myosin XV genes responsible for hereditary deafness DFNB3 and shaker 2[J].Genomics,1999,61(3):243-258..
4 Ammar-Khodja F,Bonnet C,Dahmani M,et al.Diversity of the causal genes in hearing impaired Algerian individuals identified by whole exome sequencing[J].Mol Genet Genomic Med,2015,3(3):189-196.
5 Salime S,Charif M,Bousfiha A,et al.Homozygous mutations in PJVK and MYO15A genes associated with non-syndromic hearing loss in Moroccan families[J].Int J Pediatr Otorhinolaryngol,2017,101:25-29.
6 Nal N,Ahmed ZM,Erkal E,et al.Mutational spectrum of MYO15A:the large N-terminal extension of myosin XVA is required for hearing[J].Hum Mutat,2007,28(10):1014-1019.
7 Naz S,Imtiaz A,Mujtaba G,et al.Genetic causes of moderate to severe hearing loss point to modifiers[J].Clin Genet,2017,91(4):589-598.
8 Shafique S,Siddiqi S,Schraders M,et al.Genetic spectrum of autosomal recessive non-syndromic hearing loss in Pakistani families[J].PLoS One,2014,9(6):e100146.
9 Bashir R,Fatima A,Naz S.Prioritized sequencing of the second exon of MYO15A reveals a new mutation segregating in a Pakistani family with moderate to severe hearing loss[J].Eur J Med Genet,2012,55(2):99-102.
10 Shahin H,Walsh T,Rayyan AA,et al.Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian families[J].Eur J Hum Genet,2010,18(4):407-413.
11 Friedman TB,Hinnant JT,Ghosh M,et al.DFNB3,spectrum of MYO15A recessive mutant alleles and an emerging genotype-phenotype correlation[J].Adv Otorhinolaryngol,2002,61:124-130.
12 Yan D,Tekin D,Bademci G,et al.Spectrum of DNA variants for non-syndromic deafness in a large cohort from multiple continents[J].Hum Genet,2016,135(8):953-961.
13 Atik T,Onay H,Aykut A,et al.Comprehensive Analysis of Deafness Genes in Families with Autosomal Recessive Nonsyndromic Hearing Loss[J].PLoS One,2015,10(11):e0142154.
14 Bademci G,Foster J,2nd,Mahdieh N,et al.Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort[J].Genet Med,2016,18(4):364-371.
15 Diaz-Horta O,Duman D,Foster J,2nd,et al.Whole-exome sequencing efficiently detects rare mutations in autosomal recessive nonsyndromic hearing loss[J].PLoS One,2012,7(11):e50628.
16 Duman D,Sirmaci A,Cengiz FB,et al.Screening of 38 genes identifies mutations in 62%of families with nonsyndromic deafness in Turkey[J].Genet Test Mol Biomarkers,2011,15(1-2):29-33.
17 Cengiz FB,Duman D,Sirmaci A,et al.Recurrent and private MYO15A mutations are associated with deafness in the Turkish population[J].Genet Test Mol Biomarkers,2010,14(4):543-550.
18 Kalay E,Uzumcu A,Krieger E,et al.MYO15A(DFNB3)mutations in Turkish hearing loss families and functional modeling of a novel motor domain mutation[J].Am J Med Genet A,2007,143a(20):2382-2389.
19 Motavaf M,Soveizi M,Maleki M,et al.MYO15A splicing mutations in hearing loss:A review literature and report of a novel mutation[J].Int J Pediatr Otorhinolaryngol,2017,96:35-38.
20 Sommen M,Schrauwen I,Vandeweyer G,et al.DNA Diagnostics of Hereditary Hearing Loss:A Targeted Resequencing Approach Combined with a Mutation Classification System[J].Hum Mutat,2016,37(8):812-819.
21 Sloan-Heggen CM,Babanejad M,Beheshtian M,et al.Characterising the spectrum of autosomal recessive hereditary hearing loss in Iran[J].J Med Genet,2015,52(12):823-829.
22 Fattahi Z,Shearer AE,Babanejad M,et al.Screening for MYO15A gene mutations in autosomal recessive nonsyndromic,GJB2 negative Iranian deaf population[J].Am J Med Genet A,2012,158a(8):1857-1864.
23 Shearer AE,Hildebrand MS,Webster JA,et al.Mutations in the first MyTH4 domain of MYO15A are a common cause of DF-NB3 hearing loss[J].Laryngoscope,2009,119(4):727-733.
24 Vozzi D,Morgan A,Vuckovic D,et al.Hereditary hearing loss:a96 gene targeted sequencing protocol reveals novel alleles in a series of Italian and Qatari patients[J].Gene,2014,542(2):209-216.
25 Palombo F,Al-Wardy N,Ruscone GA,et al.A novel founder MYO15A frameshift duplication is the major cause of genetic hearing loss in Oman[J].J Hum Genet,2017,62(2):259-264.
26 Riahi Z,Bonnet C,Zainine R,et al.Whole exome sequencing identifies new causative mutations in Tunisian families with non-syndromic deafness[J].PLoS One,2014,9(6):e99797.
27 Belguith H,Aifa-Hmani M,Dhouib H,et al.Screening of the DF-NB3 locus:identification of three novel mutations of MYO15Aassociated with hearing loss and further suggestion for two distinctive genes on this locus[J].Genet Test Mol Biomarkers,2009,13(1):147-151.
28 Chen JR,Tang ZH,Zheng J,et al.Effects of genetic correction on the differentiation of hair cell-like cells from iPSCs with MYO15A mutation[J].Cell Death Differ,2016,23(8):1347-1357.
29 Li W,Guo L,Li Y,et al.A novel recessive truncating mutation in MYO15A causing prelingual sensorineural hearing loss[J].Int JPediatr Otorhinolaryngol,2016,81:92-95.
30 Xia H,Huang X,Guo Y,et al.Identification of a Novel MYO15A Mutation in a Chinese Family with Autosomal Recessive Nonsyndromic Hearing Loss[J].PLoS One,2015,10(8):e0136306.
31 Chen Y,Wang Z,Wang Z,et al.Targeted next-generation sequencing in Uyghur families with non-syndromic sensorineural hearing loss[J].PLoS One,2015,10(5):e0127879.
32 Gu X,Guo L,Ji H,et al.Genetic testing for sporadic hearing loss using targeted massively parallel sequencing identifies 10novel mutations[J].Clin Genet,2015,87(6):588-593.
33 Gao X,Zhu QY,Song YS,et al.Novel compound heterozygous mutations in the MYO15A gene in autosomal recessive hearing loss identified by whole-exome sequencing[J].J Transl Med,2013,11:284.
34 Chang MY,Lee C,Han JH,et al.Expansion of phenotypic spectrum of MYO15A pathogenic variants to include postlingual onset of progressive partial deafness[J].BMC Med Genet,2018,19(1):29.
35 Jung J,Lee JS,Cho KJ,et al.Genetic Predisposition to Sporadic Congenital Hearing Loss in a Pediatric Population[J].Sci Rep,2017,7:45973.
36 Chang MY,Kim AR,Kim NK,et al.Identification and Clinical Implications of Novel MYO15A Mutations in a Non-consanguineous Korean Family by Targeted Exome Sequencing[J].Mol Cells,2015,38(9):781-788.
37 Woo HM,Park HJ,Baek JI,et al.Whole-exome sequencing identifies MYO15A mutations as a cause of autosomal recessive nonsyndromic hearing loss in Korean families[J].BMC Med Genet,2013,14:72.
38 Moteki H,Azaiez H,Booth KT,et al.Comprehensive genetic testing with ethnic-specific filtering by allele frequency in a Japanese hearing-loss population[J].Clin Genet,2016,89(4):466-472.
39 Miyagawa M,Nishio SY,Hattori M,et al.Mutations in the MYO15A gene are a significant cause of nonsyndromic hearing loss:massively parallel DNA sequencing-based analysis[J].Ann Otol Rhinol Laryngol,2015,124 Suppl 1:158s-168s.
40 Nishio SY,Usami S.Deafness gene variations in a 1120 nonsyndromic hearing loss cohort:molecular epidemiology and deafness mutation spectrum of patients in Japan[J].Ann Otol Rhinol Laryngol,2015,124 Suppl 1:49s-60s.
41 Miyagawa M,Naito T,Nishio SY,et al.Targeted exon sequencing successfully discovers rare causative genes and clarifies the molecular epidemiology of Japanese deafness patients[J].PLoSOne,2013,8(8):e71381.
42 Plevova P,Paprskarova M,Tvrda P,et al.STRC Deletion is a Frequent Cause of Slight to Moderate Congenital Hearing Impairment in the Czech Republic[J].Otol Neurotol,2017,38(10):e393-e400.
43 Baux D,Vache C,Blanchet C,et al.Combined genetic approaches yield a 48%diagnostic rate in a large cohort of French hearing-impaired patients[J].Sci Rep,2017,7(1):16783.
44 Svidnicki MC,Silva-Costa SM,Ramos PZ,et al.Screening of genetic alterations related to non-syndromic hearing loss using MassARRAY iPLEX(R)technology[J].BMC Med Genet,2015,16:85.
45 Lezirovitz K,Pardono E,de Mello Auricchio MT,et al.Unexpected genetic heterogeneity in a large consanguineous Brazilian pedigree presenting deafness[J].Eur J Hum Genet,2008,16(1):89-96.
46 Zazo Seco C,Wesdorp M,Feenstra I,et al.The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands[J].Eur J Hum Genet,2017,25(3):308-314.
47 Danial-Farran N,Brownstein Z,Gulsuner S,et al.Genetics of hearing loss in the Arab population of Northern Israel[J].Eur JHum Genet,2018,26(12):1840-1847.
48 Ma D,Shen S,Gao H,et al.A novel nonsense mutation in MYO15A is associated with non-syndromic hearing loss:a case report[J].BMC Med Genet,2018,19(1):133.
49 Zhang F,Xu L,Xiao Y,et al.Three MYO15A Mutations Identified in One Chinese Family with Autosomal Recessive Nonsyndromic Hearing Loss[J].Neural Plast,2018,2018:5898025.
50 Cabanillas R,Dineiro M,Cifuentes GA,et al.Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients[J].BMC Med Genomics,2018,11(1):58.
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