CAJ | 학술논문

目的：本研究通过总结中国感音神经性耳聋患者的致病因素，对同时携带两个基因双位点突变而导致耳聋的病例进行分析研究。方法回顾性分析4000例感音神经性耳聋患者基因突变情况，总结同时携带两个基因双位点突变而导致耳聋的病例，分析致病基因和听力表型，评估此类家庭的遗传风险。结果在4000例感音神经性耳聋患者中，发现2例耳聋患者同时携带两个基因的双位点突变。其中1例为大前庭水管综合征患者，携带SLC26A4基因的c.1229C>T(p.T410M)/c.1079C>T(p.A360V)复合杂合突变，同时携带GJB2基因c.257C>G(p.T86R)/c.299_300delAT复合杂合突变。1例患者携带GJB2基因c.235delC纯合突变，同时为线粒体DNA12S rRNA A1555G均质突变。结论对于常染色体双隐性基因双位点突变的患者，其父母再生育耳聋后代的风险将从传统的25%上升为43.75%；同时携带线粒体基因突变的耳聋患者，其母系成员则会同时携带线粒体基因突变。本研究揭示了遗传病因的复杂性。
목적：본연구통과총결중국감음신경성이롱환자적치병인소，대동시휴대량개기인쌍위점돌변이도치이롱적병례진행분석연구。방법회고성분석4000례감음신경성이롱환자기인돌변정황，총결동시휴대량개기인쌍위점돌변이도치이롱적병례，분석치병기인화은력표형，평고차류가정적유전풍험。결과재4000례감음신경성이롱환자중，발현2례이롱환자동시휴대량개기인적쌍위점돌변。기중1례위대전정수관종합정환자，휴대SLC26A4기인적c.1229C>T(p.T410M)/c.1079C>T(p.A360V)복합잡합돌변，동시휴대GJB2기인c.257C>G(p.T86R)/c.299_300delAT복합잡합돌변。1례환자휴대GJB2기인c.235delC순합돌변，동시위선립체DNA12S rRNA A1555G균질돌변。결론대우상염색체쌍은성기인쌍위점돌변적환자，기부모재생육이롱후대적풍험장종전통적25%상승위43.75%；동시휴대선립체기인돌변적이롱환자，기모계성원칙회동시휴대선립체기인돌변。본연구게시료유전병인적복잡성。
Objective Sensorineural hearing loss was reported as a single-gene disease by most studies. Here we reported two cases with pathogenic patterns in different genes.Methods 4000 patients of sensorineural hearing loss were enrolled. Types of gene mutations, and hearing levels and genetic risks were studied.Results In these 4000 patients, one patient with enlarged vestibular aqueduct was found to carry c.1229C>T(p.T410M) and c.1079C>T(p.A360V) compound heterozygous mutations in SLC26A4 gene, along with c.257C>G(p.T86R) mutation and c.299_300delAT compound heterozygous mutations in GJB2 gene. Another patient was identified to have c.235delC homogeneous mutations in GJB2 gene and A1555G homoplasmic mutation in mitochondrial 12S rRNA.Conclusion These results suggest that complicated genetic etiologies in these two cases had an impact on the diagnostic strategy for hereditary hearing impairment. The recurrent risk for patients’ siblings and offspring will be changed. For one patient, the recurrent risks of hearing impairment will increase up to 43.75% from 25%. The other patient has siblings and offspring who will carry mitochondrial DNA A1555G mutation and 25% of her sibling may have the same homozygous GJB2 c.235delC mutations. This will have great impact on genetic counseling and risk prediction.