Al-Qahtani Mohammed H, Baghlab Ibtessam, Chaudhary Adeel G, Abuzenadah Adel M, Bamanie Afaf, Daghistani Kamal J, Safieh Malek, Fida Loai, Dallol Ashraf
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
Genet Test Mol Biomarkers. 2010 Feb;14(1):79-83. doi: 10.1089/gtmb.2009.0111.
Nonsyndromic hearing loss (NSHL) affects a substantial proportion of newborns in the world every year. This proportion increases proportionally with the degree of consanguineous marriages in any society. In the Kingdom of Saudi Arabia, consanguineous marriages are common practice and this is associated with a noticeably high frequency of inherited conditions affecting the resulting progeny, including NSHL. Until now there is no published data on the genetic causes of NSHL in Saudi Arabia, which greatly hindered the ability of local genetic counseling and family planning centers to distinguish between hereditary and nonhereditary forms of NSHL and subsequently could not give information on the possible inheritance of deafness. In addition, the lack of validated genetic tests for NSHL delayed the detection of deafness in affected individuals and may have lowered the efficiency of later medical interventions. Further, the population covered in this study is likely to have a multiethnic background caused by decades of religious and economic migration to this region. To address such problems, we undertook the task of unraveling the genetic causes of hearing loss in Saudi Arabia, starting with identifying the GJB2/DFNB1 mutation spectrum in a cohort of unrelated individuals suffering from mild to profound NSHL. A total of 12 reported GJB2 mutations were identified in 17 out of 109 (15.59%) NSHL cases. Biallelic GJB2 mutations were identified in 11 out of the 109 NSHL cases (10.09%), with c.35delG being the most common (7/11, 63.63%). The remaining six patients were found to have monoallelic GJB2 mutations. Interestingly, biallelic GJB2 mutations were not detected in patients of Arab tribal origins, reflecting the genetic heterogeneity of the western area of the Kingdom of Saudi Arabia. Therefore, ethnically targeted genetic screening for GJB2 mutations could be a useful tool toward the management of NSHL in this area.
每年，非综合征性听力损失（NSHL）影响着全球相当一部分新生儿。这一比例会随着任何社会中近亲结婚程度的增加而相应上升。在沙特阿拉伯王国，近亲结婚很常见，这与影响后代的遗传性疾病（包括NSHL）的高发病率显著相关。到目前为止，尚无关于沙特阿拉伯NSHL遗传病因的公开数据，这极大地阻碍了当地遗传咨询和计划生育中心区分NSHL的遗传和非遗传形式的能力，进而无法提供关于耳聋可能遗传情况的信息。此外，缺乏经过验证的NSHL基因检测方法延误了对受影响个体耳聋的检测，可能还降低了后续医疗干预的效率。此外，由于数十年来宗教和经济移民涌入该地区，本研究涵盖的人群可能具有多种族背景。为了解决这些问题，我们承担了一项任务，即从确定一组患有轻度至重度NSHL的无关个体中的GJB2/DFNB1突变谱开始，来揭示沙特阿拉伯听力损失的遗传病因。在109例NSHL病例中的17例（15.59%）中，共鉴定出12种已报道的GJB2突变。在109例NSHL病例中的11例（10.09%）中鉴定出双等位基因GJB2突变，其中c.35delG最为常见（7/11，63.63%）。其余6例患者被发现有单等位基因GJB2突变。有趣的是，在阿拉伯部落出身的患者中未检测到双等位基因GJB2突变，这反映了沙特阿拉伯王国西部地区的遗传异质性。因此，针对特定种族的GJB2突变基因筛查可能是该地区NSHL管理的有用工具。
