Abstract：
BACKGROUND: Despite the high genetic heterogeneity of hearing loss, mutations in the GJB2 gene are a major cause of autosomal recessive nonsyndromic hearing loss (NSHL) worldwide. However, the mutation profile of GJB2 in NSHL is under-investigated in Morocco, especially among simplex cases. This study aimed to identify the spectrum and frequency of GJB2 mutations in the Moroccan population among simplex and multiplex families with NSHL.
METHODS: Moroccan families with NSHL were selected according to well-defined criteria. Selected families were screened for GJB2 gene variants using direct sequencing of the entire coding region of GJB2.
RESULTS: A total of 145 affected individuals from 115 families with NSHL were included in this study (49 simplex, 66 multiplex). Mutations in the GJB2 gene were noted in 28.69% of the families (33/115), of which 75.75% were multiplex families and 24.24% were simplex. In total, seven different mutations were detected: c.35delG(p.G12fs), c.551G>A(p.R184Q), c.139G>T(p.E47X), c.109G>A(p.V37I), c.167delT(p.L56fs), c.617A>G(p.N206S), c.94C>T(p.R32C). The last three mutations have not previously been reported in Morocco. The most common GJB2 mutation was c.35delG (21.73%), followed by p.V37I (2.60%) and p.E47X (1.73%).
CONCLUSIONS: Our study confirms a high prevalence of GJB2 variants in the Moroccan population, particularly the c.35delG mutation. Additionally, we have identified previously unreported or rarely reported mutations, revealing a greater diversity of GJB2 mutations. These findings emphasize the importance of comprehensive screening beyond the 35delG mutation for patients with NSHL, regardless of their family history. Integrating this approach into clinical care will enhance diagnosis and management of hearing loss in the Moroccan population.
METHODS: Moroccan families with NSHL were selected according to well-defined criteria. Selected families were screened for GJB2 gene variants using direct sequencing of the entire coding region of GJB2.
RESULTS: A total of 145 affected individuals from 115 families with NSHL were included in this study (49 simplex, 66 multiplex). Mutations in the GJB2 gene were noted in 28.69% of the families (33/115), of which 75.75% were multiplex families and 24.24% were simplex. In total, seven different mutations were detected: c.35delG(p.G12fs), c.551G>A(p.R184Q), c.139G>T(p.E47X), c.109G>A(p.V37I), c.167delT(p.L56fs), c.617A>G(p.N206S), c.94C>T(p.R32C). The last three mutations have not previously been reported in Morocco. The most common GJB2 mutation was c.35delG (21.73%), followed by p.V37I (2.60%) and p.E47X (1.73%).
CONCLUSIONS: Our study confirms a high prevalence of GJB2 variants in the Moroccan population, particularly the c.35delG mutation. Additionally, we have identified previously unreported or rarely reported mutations, revealing a greater diversity of GJB2 mutations. These findings emphasize the importance of comprehensive screening beyond the 35delG mutation for patients with NSHL, regardless of their family history. Integrating this approach into clinical care will enhance diagnosis and management of hearing loss in the Moroccan population.
摘要：
背景：尽管听力损失具有很高的遗传异质性，GJB2基因突变是全球常染色体隐性遗传非综合征性听力损失(NSHL)的主要原因.然而,在摩洛哥，NSHL中GJB2的突变谱研究不足，尤其是在单纯形案例中。这项研究旨在确定NSHL单纯形和多重家族中摩洛哥人群中GJB2突变的频谱和频率。
方法：根据明确的标准选择患有NSHL的摩洛哥家庭。使用GJB2的整个编码区的直接测序筛选所选择的家族的GJB2基因变体。
结果：这项研究共纳入了来自115个患有NSHL的家庭的145个受影响的个体(49个单纯形，66多重）。在28.69％的家族（33/115）中注意到GJB2基因的突变，其中75.75%为多元家族，24.24%为单纯性。总的来说,检测到七个不同的突变：c.35delG（p。G12fs),c.551G>A（第R184Q),c.139G>T(p.E47X),c.109G>A（p。V37I),c.167delT（p.L56fs),c.617A>G（第N206S),c.94C>T（p。R32C)。最后三个突变以前在摩洛哥没有报道过。最常见的GJB2突变是c.35delG(21.73%),其次是p.V37I（2.60%）和p.E47X（1.73%）。
结论：我们的研究证实了摩洛哥人群中GJB2变体的高患病率，尤其是c.35delG突变.此外,我们已经确定了以前未报告或很少报告的突变，揭示了GJB2突变的更大多样性。这些发现强调了对NSHL患者进行超越35delG突变的全面筛查的重要性。不管他们的家族史。将这种方法纳入临床护理将增强摩洛哥人群听力损失的诊断和管理。
方法：根据明确的标准选择患有NSHL的摩洛哥家庭。使用GJB2的整个编码区的直接测序筛选所选择的家族的GJB2基因变体。
结果：这项研究共纳入了来自115个患有NSHL的家庭的145个受影响的个体(49个单纯形，66多重）。在28.69％的家族（33/115）中注意到GJB2基因的突变，其中75.75%为多元家族，24.24%为单纯性。总的来说,检测到七个不同的突变：c.35delG（p。G12fs),c.551G>A（第R184Q),c.139G>T(p.E47X),c.109G>A（p。V37I),c.167delT（p.L56fs),c.617A>G（第N206S),c.94C>T（p。R32C)。最后三个突变以前在摩洛哥没有报道过。最常见的GJB2突变是c.35delG(21.73%),其次是p.V37I（2.60%）和p.E47X（1.73%）。
结论：我们的研究证实了摩洛哥人群中GJB2变体的高患病率，尤其是c.35delG突变.此外,我们已经确定了以前未报告或很少报告的突变，揭示了GJB2突变的更大多样性。这些发现强调了对NSHL患者进行超越35delG突变的全面筛查的重要性。不管他们的家族史。将这种方法纳入临床护理将增强摩洛哥人群听力损失的诊断和管理。
