Identification of a MYO7A mutation in a large Chinese DFNA11 family and genotype–phenotype review for DFNA11

Abstract

Background: The molecular and genetic research showed the association between DFNA11 and mutations in MYO7A. This research aimed to identify a MYO7A mutation in a family with nonsyndromic autosomal dominant hearing loss.

Methods: We have ascertained one large multigenerational Chinese family (Z029) with autosomal dominant late-onset progressive non-syndromic sensorineural hearing loss. Genome-wide linkage analysis of the family mapped the disease locus to the DFNA11 interval, where the MYO7A was considered as a candidate gene. Sequencing of the PCR products was carried out for each sample. One hundred and fifty one control subjects with normal hearing functions were also evaluated.

Results: The pathogenic mutation (c.2011G>A) was identified in the family. This mutation co-segregated with hearing loss in this family. No mutation of MYO7A gene was found in the 151 controls.

Conclusions: The missense mutation of MYO7A is identified in the family displaying the pedigree consistent with DFNA11. We not only examined the clinical and genetic characteristics of the family, but also provided a basis for genetic counseling. We also summarized and analyzed the phenotypes and genotypes of all DFNA11 families, four of nine are Chinese families, suggesting that MYO7A mutations are not rare. Therefore, we should pay more attention to Chinese patients.

Chinese abstract

背景：分子学和基因学研究显示出DFNA11与MYO7A突变之间的关联。这项研究旨在确定一个具有非综合征性常染色体显性遗传性耳聋的家族中的MYO7A突变。

方法：我们已经确定了一个具有常染色体显性迟发性进展型非综合征型感音神经性耳聋的多代中国大家庭（Z029）。对这个家族的全基因组连锁分析将疾病基因座定位于DFNA11区间, 其中MYO7A被认为是候选基因。对每个样品进行PCR产物的测序。还评估了一百五十一名听力正常的对照受试者。

结果：该家族中发现了致病突变（c.2011G > A）。这个突变与这个家族中的听力损失同时分离 。在151个对照者中没有发现MYO7A基因的突变。

结论：显示与DFNA11一致的血统的家族中鉴别出MYO7A的错义突变。我们不仅检查了家族的临床和遗传特征, 而且为遗传咨询提供了基础。我们还总结和分析了所有DFNA11家族的表型和基因型, 9个家族中有4个是中国家族, 这表明MYO7A突变在中国家族中并不罕见。因此, 我们应该更多地关注中国患者。

Keywords:

• DFNA11
• MYO7A
• mutation
• hearing loss
• review

Acknowledgements

We thank the family for their invaluable cooperation and participation. We thank all colleagues in ENT departments who provided the patient samples. We thank Cui Zhao for DNA extraction and MYO7A gene screening.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the grants of the National Key Basic Research Program of China (No. 2014CB943001), the National Natural Science Foundation of China (No. 81120108009 and 81530032).