LHFPL5基因相关遗传性听力损失研究进展

Research progress on hereditary hearing loss associated with LHFPL5 gene

白雪晶;叶丹;朱莹;张春婷;徐文波

1:玉溪市人民医院

摘要
LHFPL5基因参与耳蜗毛细胞机电传导过程,在维持听觉和平衡功能中起重要作用。本综述旨在探讨LHFPL5基因及其相关蛋白引起听力损失的病理机制。综合国内外相关文献,分析LHFPL5基因突变导致听力损失的特征,探讨LHFPL5基因致聋的分子病因,为中国听障人群是否需要进行LHFPL5基因筛查提供依据,并为后续基础研究和临床诊治提供理论指导。
关键词
LHFPL5基因;四跨膜蛋白;跨膜通道样蛋白1;原钙粘蛋白15
基金项目(Foundation):
云南省科技厅-昆明医科大学应用基础研究联合专项资金(202101AY070001-202)
作者
白雪晶;叶丹;朱莹;张春婷;徐文波
参考文献

[1] SHABBIR M I,AHMED Z M,KHAN S Y,et al.Mutations of human tmhs cause recessively inherited non-syndromic hearing loss[J].J Med Genet,2006,43(8):634-640.

[2] ERICKSON T,PACENTINE I V,VENUTO A,et al.The lhfpl5 ohnologs lhfpl5a and lhfpl5b are required for mechanotransduction in distinct populations of sensory hair cells in zebrafish[J].Frontiers in Molecular Neuroscience,2023,12:320.DOI:10.3389/fnmol.2019.00320.

[3] SOLER D C,BALLESTEROS A,SLOAN A E,et al.Multiple plasma membrane reporters discern lhfpl5 region that blocks trafficking to the plasma membrane[J].Sci Rep,2023,13(1):2528.DOI:10.1038/s41598-023-28045-w.

[4] RAYAT S,FARHADI M,EMAMDJOMEH H,et al.Analysis of tmie gene mutations including the first large deletion of exon 1 with autosomal recessive non-syndromic deafness[J].BMC Med Genomics,2022,15(1):133.DOI:10.1186/s12920-022-01287-9.

[5] PEPERMANS E,PETIT C.The tip-link molecular complex of the auditory mechano-electrical transduction machinery[J].Hearing Res,2015,330(Pt A):10-17.

[6] XIONG W,GRILLET N,ELLEDGE H,et al.Tmhs is an integral component of the mechanotransduction machinery of cochlear hair cells[J].Cell,2012,151(6):1283-1295.

[7] BEURG M,XIONG W,ZHAO B,et al.Subunit determination of the conductance of hair-cell mechanotransducer channels[J].P Natl Acad Sci USA,2014,112(5):1589-1594.

[8] MAEDA R,KINDT K S,MO W,et al.Tip-link protein protocadherin 15 interacts with transmembrane channel-like proteins tmc1 and tmc2[J].P Natl Acad Sci USA,2014,111(35):12907-12912.

[9] KAWASHIMA Y,GéLéOC G S,KURIMA K,et al.Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes[J].J Clin Invest,2011,121(12):4796-4809.

[10] YU X J,ZHAO Q R,LI X F,et al.Deafness mutation D572N of tmc1 destabilizes tmc1 expression by disrupting lhfpl5 binding[J].P Natl Acad Sci USA,2020,117(47):29894-29903.

[11] LONGO-GUESS C M,GAGNON L H,FRITZSCH B,et al.Targeted knockout and lacz reporter expression of the mouse tmhs deafness gene and characterization of the hscy-2j mutation[J].Mamm Genome,2007,18(9):646-656.

[12] GE J,ELFERICH J,GOEHRING A,et al.Structure of mouse protocadherin 15 of the stereocilia tip link in complex with lhfpl5[J].Elife,2018,7:e38700.DOI:10.7554/eLife.38770

[13] GRILLET N,KAZMIERCZAK P,XIONG W,et al.The mechanotransduction machinery of hair cells[J].Sci Signal,2009,2(85):pt5.DOI:10.1126/scisignal.285pt5.

[14] KAZMIERCZAK P,SAKAGUCHI H,TOKITA J,et al.Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells[J].Nature,2007,449(7158):87-91.

[15] KALAY E,LI Y,UZUMCU A,et al.Mutations in the lipoma hmgic fusion partner-like 5 (lhfpl5) gene cause autosomal recessive nonsyndromic hearing loss[J].Hum Mutat,2006,27(7):633-639.

[16] SHAHIN H,WALSH T,RAYYAN A A,et al.Five novel loci for inherited hearing loss mapped by snp-based homozygosity profiles in palestinian families[J].Eur J Hum Genet,2009,18(4):407-418.

[17] BENSA?D M,HMANI-AIFA M,HAMMAMI B,et al.DFNB66 and DFNB67 loci are non allelic and rarely contribute to autosomal recessive nonsyndromic hearing loss[J].Eur J Med Genet,2011,54(6):e565-9.

[18] 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.

[19] LERAT J,BONNET C,CARTAULT F,et al.High prevalence of congenital deafness on reunion island is due to a founder variant of lhfpl5[J].Clin Genet,2018,95(1):177-181.

[20] LIAQAT K,CHIU I,LEE K,et al.Novel missense and 3′-UTR splice site variants in lhfpl5 cause autosomal recessive nonsyndromic hearing impairment[J].J Hum Genet,2018,63(11):1099-1107.

[21] SHANG H,YAN D,TAYEBI N,et al.Targeted next-generation sequencing of a deafness gene panel (miamiotogenes) analysis in families unsuitable for linkage analysis[J].Biomed Res Int,2018,3103986.DOI:10.1155/2018/3103986.

[22] AL-AMRI A H,AL-SAEGH A,AL-MAMARI W,et al.Lhfpl5 mutation:a rare cause of non-syndromic autosomal recessive hearing loss[J].Eur J Med Genet,2018,62(12):103592.DOI:10.1016/j.ejmg.2018.11.026.

[23] MEHREGAN H,MOHSENI M,AKBARI M,et al.Novel mutations in kcnq4,lhfpl5 and coch genes in iranian families with hearing impairment[J].Arch Iran Med,2019,22(4):189-197.