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Abstract：
OBJECTIVE: Hearing impairment is the most common sensorineural disorder and is genetically heterogeneous. Identification of the pathogenic mutations underlying hearing impairment is difficult, since causative mutations in 127 different genes have so far been reported.
METHODS: In this study, we performed Next-generation sequencing (NGS) in 2 individuals from a consanguineous family with hearing loss.
RESULTS: Three novel mutations in known deafness genes were identified in the family; MYO6-p.R928C and -p.D1223N in heterozygous state and ILDR1-p.Y143C in homozygous state. Sanger sequencing confirmed co-segregation of the three mutations with deafness in the family. The identified mutation in ILDR1 gene is located in the immunoglobulin-type domain of the ILDR1 protein and the detected mutations in MY06 are located in the tail domain of the MYO6 protein. The mutations are predicted to be pathogenic by SIFT, PolyPhen and Mutation Taster.
CONCLUSIONS: Our results suggest that either the homozygous ILDR1-p.Y143C mutation might be the pathogenic variant for ARNSHL or heterozygous MYO6- p.R928C, -p.D1223N might be involved in these patient\'s disorder due to compound heterozygousity. To our knowledge, this is the first ILDR1 and MYO6 mutations recognized in the southwest Iran. Our data expands the spectrum of mutations in ILDR1 and MYO6 genes.
METHODS: In this study, we performed Next-generation sequencing (NGS) in 2 individuals from a consanguineous family with hearing loss.
RESULTS: Three novel mutations in known deafness genes were identified in the family; MYO6-p.R928C and -p.D1223N in heterozygous state and ILDR1-p.Y143C in homozygous state. Sanger sequencing confirmed co-segregation of the three mutations with deafness in the family. The identified mutation in ILDR1 gene is located in the immunoglobulin-type domain of the ILDR1 protein and the detected mutations in MY06 are located in the tail domain of the MYO6 protein. The mutations are predicted to be pathogenic by SIFT, PolyPhen and Mutation Taster.
CONCLUSIONS: Our results suggest that either the homozygous ILDR1-p.Y143C mutation might be the pathogenic variant for ARNSHL or heterozygous MYO6- p.R928C, -p.D1223N might be involved in these patient\'s disorder due to compound heterozygousity. To our knowledge, this is the first ILDR1 and MYO6 mutations recognized in the southwest Iran. Our data expands the spectrum of mutations in ILDR1 and MYO6 genes.
摘要：
目的：听力障碍是最常见的感觉神经性疾病，具有遗传异质性。很难识别听力障碍的致病突变，因为迄今为止已经报道了127个不同基因的致病突变。
方法：在本研究中，我们对来自一个听力损失近亲家庭的2名个体进行了下一代测序(NGS).
结果：在该家族中发现了已知耳聋基因中的三个新突变；MYO6-p。R928C和-p。杂合状态的D1223N和ILDR1-p。Y143C处于纯合状态。Sanger测序证实了家族中三种突变与耳聋的共分离。ILDR1基因中鉴定的突变位于ILDR1蛋白的免疫球蛋白型结构域中,并且MY06中检测到的突变位于MYO6蛋白的尾部结构域中。SIFT预测突变是致病的，PolyPhen和突变品尝者。
结论：我们的结果表明纯合ILDR1-p。Y143C突变可能是ARNSHL或杂合MYO6-p.R928C的致病变异，-p.由于复合杂合性，D1223N可能与这些患者的疾病有关。据我们所知,这是伊朗西南部地区首次发现的ILDR1和MYO6基因突变。我们的数据扩展了ILDR1和MYO6基因的突变谱。
方法：在本研究中，我们对来自一个听力损失近亲家庭的2名个体进行了下一代测序(NGS).
结果：在该家族中发现了已知耳聋基因中的三个新突变；MYO6-p。R928C和-p。杂合状态的D1223N和ILDR1-p。Y143C处于纯合状态。Sanger测序证实了家族中三种突变与耳聋的共分离。ILDR1基因中鉴定的突变位于ILDR1蛋白的免疫球蛋白型结构域中,并且MY06中检测到的突变位于MYO6蛋白的尾部结构域中。SIFT预测突变是致病的，PolyPhen和突变品尝者。
结论：我们的结果表明纯合ILDR1-p。Y143C突变可能是ARNSHL或杂合MYO6-p.R928C的致病变异，-p.由于复合杂合性，D1223N可能与这些患者的疾病有关。据我们所知,这是伊朗西南部地区首次发现的ILDR1和MYO6基因突变。我们的数据扩展了ILDR1和MYO6基因的突变谱。
