GJB2 基因突变患者听力学结局预测模型。

Prediction Model for Audiological Outcomes in Patients With GJB2 Mutations.

机构信息

Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.

Department of Otolaryngology, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan.

出版信息

Ear Hear. 2020 Jan/Feb;41(1):143-149. doi: 10.1097/AUD.0000000000000742.

DOI:10.1097/AUD.0000000000000742

PMID:31246659

Abstract

OBJECTIVES

Recessive mutations in GJB2 are the most common genetic cause of sensorineural hearing impairment (SNHI) in humans. SNHI related to GJB2 mutations demonstrates a wide variation in audiological features, and there has been no reliable prediction model for hearing outcomes until now. The objectives of this study were to clarify the predominant factors determining hearing outcome and to establish a predictive model for SNHI in patients with GJB2 mutations.

DESIGN

A total of 434 patients confirmed to have biallelic GJB2 mutations were enrolled and divided into three groups according to their GJB2 genotypes. Audiological data, including hearing levels and audiogram configurations, were compared between patients with different genotypes. Univariate and multivariate generalized estimating equation (GEE) analyses were performed to analyze longitudinal data of patients with multiple audiological records.

RESULTS

Of the 434 patients, 346 (79.7%) were homozygous for the GJB2 p.V37I mutation, 55 (12.7%) were compound heterozygous for p.V37I and another GJB2 mutation, and 33 (7.6%) had biallelic GJB2 mutations other than p.V37I. There was a significant difference in hearing level and the distribution of audiogram configurations between the three groups. Multivariate GEE analyses on 707 audiological records of 227 patients revealed that the baseline hearing level and the duration of follow-up were the predominant predictors of hearing outcome, and that hearing levels in patients with GJB2 mutations could be estimated based on these two parameters: (Predicted Hearing Level [dBHL]) = 3.78 + 0.96 × (Baseline Hearing Level [dBHL]) + 0.55 × (Duration of Follow-Up [y]).

CONCLUSION

The baseline hearing level and the duration of follow-up are the main prognostic factors for outcome of GJB2-related SNHI. These findings may have important clinical implications in guiding follow-up protocols and designing treatment plans in patients with GJB2 mutations.

摘要

目的

GJB2 中的隐性突变是人类感音神经性听力损失（SNHI）最常见的遗传原因。与 GJB2 突变相关的 SNHI 在听力学特征上表现出广泛的变异性，迄今为止，还没有可靠的听力结果预测模型。本研究的目的是阐明决定听力结果的主要因素，并为 GJB2 突变患者的 SNHI 建立预测模型。

设计

共纳入 434 例经证实存在 GJB2 双等位基因突变的患者，并根据 GJB2 基因型分为三组。比较不同基因型患者的听力学数据，包括听力水平和听力图类型。对具有多次听力记录的患者进行单变量和多变量广义估计方程（GEE）分析。

结果

434 例患者中，346 例（79.7%）为 GJB2 p.V37I 突变纯合子，55 例（12.7%）为 p.V37I 与另一种 GJB2 突变的复合杂合子，33 例（7.6%）为 GJB2 突变除 p.V37I 以外的双等位基因。三组间听力水平和听力图类型分布存在显著差异。对 227 例患者的 707 份听力记录进行多变量 GEE 分析显示，基线听力水平和随访时间是听力结果的主要预测因素，根据这两个参数可估计 GJB2 突变患者的听力水平：（预测听力水平[dBHL]）= 3.78 + 0.96×（基线听力水平[dBHL]）+ 0.55×（随访时间[y]）。