Exome sequencing in infants with congenital hearing impairment: a population-based cohort study
Exome sequencing in infants with congenital hearing impairment: a population-based cohort study
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DOI：
10.1038/s41431-019-0553-8
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发表时间：
2020-05-01
影响因子：
5.2
通讯作者：
Amor, David J.
中科院分区：
文献类型：
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作者：
Downie, Lilian;Halliday, Jane;Amor, David J.
先天性听力障碍（HI）是最常见的感觉障碍，可以是孤立的，也可以是综合征的一部分。在澳大利亚，通过新生儿听力筛查进行诊断，通过早期干预、助听器和人工耳蜗植入进行管理已得到很好的确立;然而，对先天性HI的遗传基础的了解一直缺失。该人群衍生队列包括2016-2017日历年出生的中度-重度双侧HI婴儿，通过新生儿听力筛查检测到。参与者通过综合儿科，耳鼻喉科和遗传学HI诊所招募，并在HiSeq 4000或NextSeq 500（Illumina）平台上提供全外显子组测序（WES），目标平均测序深度为100 x，并在Illumina Infinium核心外显子组-24v1.2平台上提供染色体微阵列。在接触的患者中，68%（106/156）同意参与。基因诊断率为56%（59/106），显著高于标准治疗（仅GJB 2/6测序）的21%（22/106）。对106名参与者有临床意义：36%不需要进一步筛查，9%进行了定制筛查，2%接受了治疗，4%接受了复杂神经发育综合征的知情护理。该队列中的WES证实了与先天性HI相关的诊断范围，并证实了先天性HI的遗传异质性。高诊断率和临床意义强调了基因组测序成为护理标准的必要性。
Congenital hearing impairment (HI) is the most common sensory impairment and can be isolated or part of a syndrome. Diagnosis through newborn hearing screening and management through early intervention, hearing aids and cochlear implantation is well established in the Australian setting; however understanding the genetic basis of congenital HI has been missing. This population-derived cohort comprised infants with moderate-profound bilateral HI born in the 2016-2017 calendar years, detected through newborn hearing screening. Participants were recruited through an integrated paediatric, otolaryngology and genetics HI clinic and offered whole exome sequencing (WES) on a HiSeq4000 or NextSeq500 (Illumina) platform with a targeted average sequencing depth of 100x and chromosome microarray on the Illumina Infinium core exome-24v1.2 platform. Of those approached, 68% (106/156) consented to participate. The rate of genetic diagnosis was 56% (59/106), significantly higher than standard of care (GJB2/6 sequencing only), 21% (22/106). There were clinical implications for the 106 participants: 36% required no further screening, 9% had tailored screening initiated, 2% were offered treatment and 4% had informed care for a complex neurodevelopmental syndrome. WES in this cohort demonstrates the range of diagnoses associated with congenital HI and confirms the genetic heterogeneity of congenital HI. The high diagnostic yield and clinical implications emphasises the need for genomic sequencing to become standard of care.