背景:MPZL2的突变,常染色体隐性遗传耳聋位点111(DFNB111)的特征性遗传病因,引起非综合征性和中度感音神经性听力损失。
方法:在本研究中,我们分析了8个家系的表型和基因型,这些家系由10名患有MPZL2双等位基因致病或可能致病变异的听力损失患者组成.这些患者是从3272名接受基因检测的中国患者队列中确定的。
结果:除了对称和中度感觉神经性听力损失,MPZL2相关表型的特征是进行性听力损失,其发病年龄存在差异(先天性缺陷至年轻成人阶段发病).我们确定在中国人口中,在诊断为听力损失的患者中,MPZL2缺陷的遗传负荷为0.24%(8/3272),在诊断为由STRC引起的遗传性中度感音神经性听力损失的患者中,MPZL2缺陷的遗传负荷为7.02%(8/114)。OTOA,OTOG,OTOGL,TECTA,MPZL2等。三种已知的MPZL2变体(c.220C>T(p。Gln74*),c.68delC(p.Pro23Leufs*2),c.463delG(p。Ala155Leufs*10))和一个新颖的开始损失变体(c.3G>T(p。Met1?)))被确定。与c.72delA相比,MPZL2c.220C>T被确定为中国人群甚至东亚的热点变体(p。Ile24Metfs*22)在欧洲和西亚经由过程等位基因频率。
结论:我们得出的结论是,除了中度HL,渐进式HL是MPZL2相关HL的另一个特征。对于HL的进展,没有验证指定的变体,外显度和表现力还不能确定。鉴定了起始密码子处的新型MPZL2变体,丰富了MPZL2的变异谱。MPZL2的热点变体在不同种族中有所不同。本研究为诊断提供了有价值的数据,与MPZL2相关的中度感音神经性耳聋患者的预后评估和遗传咨询。
BACKGROUND: Mutations in MPZL2, the characteristic genetic etiology of autosomal recessive deafness loci 111 (DFNB111), cause non-syndromic and moderate sensorineural hearing loss.
METHODS: In this study, we analyzed the phenotype and genotype of eight pedigrees consisting of 10 hearing loss patients with bi-allelic pathogenic or likely pathogenic variants in MPZL2. These patients were identified from a 3272 Chinese patient cohort who underwent genetic testing.
RESULTS: Apart from symmetrical and moderate sensorineural hearing loss, the MPZL2-related phenotype was characterized by progressive hearing loss with variation in the onset age (congenital defect to onset at the young adult stage). We determined that in the Chinese population, the genetic load of MPZL2 defects was 0.24% (8/3272) in patients diagnosed with hearing loss and 7.02% (8/114) in patients diagnosed with hereditary moderate sensorineural hearing loss caused by STRC, OTOA, OTOG, OTOGL, TECTA, MPZL2 and others. Three known MPZL2 variants (c.220C > T (p.Gln74*), c.68delC (p.Pro23Leufs*2), c.463delG (p.Ala155Leufs*10)) and a novel start loss variant (c.3G > T (p.Met1?)) were identified. MPZL2 c.220C > T was identified as the hotspot variant in the Chinese population and even in East Asia compared with c.72delA (p.Ile24Metfs*22) in European and West Asia through allele frequency.
CONCLUSIONS: We concluded that apart from moderate HL, progressive HL is another character of MPZL2-related HL. No specified variant was verified for the progression of HL, the penetrance and expressivity cannot be determined yet. A novel MPZL2 variant at the start codon was identified, enriching the variant spectrum of MPZL2. The hotspot variants of MPZL2 vary in different ethnicities. This study provides valuable data for the diagnosis, prognosis evaluation and genetic counseling of patients with moderate sensorineural hearing loss related to MPZL2.