背景:遗传性听力损失是先天性听力损失的重要组成部分。MARVELD2(OMIMID:610572),位于DFNB49基因座,它编码一种紧密连接蛋白三细胞蛋白,在内耳的感觉上皮屏障中起重要作用,可能导致非综合征性常染色体隐性遗传性听力损失。
方法:对2个中国汉族听力损失家系进行了临床和遗传学分析。通过靶向下一代测序检测变异体,并将测序数据与人类基因组参考(GRCh37/hg19)进行比较以鉴定突变基因和基因座。此外,在线工具,如RDDC,SpliceAI,和REVEL用于预测不同变异的风险。
结果:两个先证者均未通过新生儿听力筛查,并被诊断为感音神经性听力损失。在这两个家族中共检测到3个突变,c.1331+1G>A,c.1325A>G,和c.782G>A.根据ACMG/AMP指南,他们被认为是致病性的,不确定的意义,和不确定的意义,分别。
结论:这些发现有助于更好地理解MARVELD2的不同变体与听力之间的关系。这可以进一步扩大耳聋基因突变的范围,并有助于耳聋患者的管理和遗传咨询。
BACKGROUND: Hereditary hearing loss is an important component of congenital hearing loss. MARVELD2 (OMIM ID:610572), located in the DFNB49 locus, which encodes a tight junction protein tricellulin playing an important role in the sensory epithelial barrier of the inner ear, may contribute to nonsyndromic autosomal recessive hereditary hearing loss.
METHODS: Two Han Chinese pedigrees with hearing loss underwent clinical and genetic analyses. Variants were detected by targeted next-generation sequencing and sequencing data were compared with the Human Genome Reference (GRCh 37/hg 19) to identify mutant genes and loci. Furthermore, online tools such as RDDC, SpliceAI, and REVEL were used to predict risks from different variants.
RESULTS: Both two probands failed neonatal hearing screening and were diagnosed with sensorineural hearing loss. A total of 3 mutations were detected in the two families, c.1331+1G>A, c.1325A>G, and c.782G>A. According to ACMG/AMP guidelines, they were judged to be pathogenic, uncertain significance, and uncertain significance, respectively.
CONCLUSIONS: These findings contribute to a better understanding of the relationship between different variants of MARVELD2 and hearing. This could further expand the spectrum of deafness gene mutations and contribute to deafness patient management and genetic counseling.