Familial nonsyndromic hearing loss with incomplete partition type II caused by novel DSPP gene mutations

Abstract

Background: Familial nonsyndromic hearing loss (NSHL) with incomplete partition type II (IP-II) is a very rare condition.

Aims/Objectives: To determine the audiological feature, inheritance patterns and genetic etiology of familial NSHL with IP-II in a Chinese family with eight family members.

Material and methods: Clinical data were collected from all eight family members, selected deafness genes were sequenced in proband and whole genome sequencing of seven family members was performed.

Results: The proband were a pair of male nonidentical twins (III:1, III:2). Three patients in this family, including the twins and their father (II:1), were diagnosed with bilateral NSHL with IP-II, and no mutation was found in the genes of SLC26A4, GJB2, GJB3, mitochondrial 12S rRNA, and MITF. Whole genome sequencing data indicated de novo mutations of the gene DSPP, c.3085A > G and c.3087C > T, which resulted in p.N1029D and co-segregated with deafness phenotype, were the underlying genetic etiology.

Conclusion and significance: Familial NSHL with IP-II is extremely rare. In this family, de novo DSPP gene mutations, were considered to be the most probable genetic etiology. And this is the first report to reveal DSPP gene mutations leading to familial NSHL with IP-II.

Chinese abstract

背景：不完全类II型（IP-II）家族性非综合征性听力丧失（NSHL）是一种非常罕见的疾病。

目的：研究中国的一个八口之家的IP-II家族性NSHL的听力学特征、遗传模式和遗传病因。

材料和方法：从所有8个家庭成员处收集临床数据, 对所选先证者的耳聋基因进行测序并对其余7个家庭成员进行全基因组测序。

结果：先证者是一对男性非相象双胞胎（III：1, III：2）。包括双胞胎及其父亲在内的3名患者（II：1）被诊断出患有IP-II两侧NSHL, 而且在SLC26A4、GJB2、GJB3、线粒体12S rRNA和MITF的基因中未发现突变。全基因组测序数据表现出基因DSPP的新生突变（c.3085A > G和c.3087C > T）, 是它们导致p.N1029D, 并与耳聋表型共分离, 说明其遗传性病因。

结论和意义：具有IP-II的家族性NSHL极为罕见。在这种家族中, 新生DSPP基因突变被认为是最可能的遗传性病因。这是揭示DSPP基因突变导致IP-II家族性NSHL的首次报道。

Keywords:

• Nonsyndromic hearing loss
• familial incomplete partition type II
• DSPP gene mutations

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work was supported by National Natural Science Foundation of China under grants [Number 81670940, 81670941, 81570933, and 81400472]; Special Cultivating and Developing Program of Beijing Science and Technology Innovation Base under grant [z151100001615050]; China Postdoctoral Science Foundation under grant [2014M552649]; Suzhou’s Key Discipline of Medicine under grant [SZXK201503]; and Jiangsu Provincial Commission of Health and Family Planning under grant [H2017061].