Kim Shin Hye, Kim Ah Reum, Choi Hyun Seok, Kim Min Young, Chun Eun Hi, Oh Seung-Ha, Choi Byung Yoon
From the Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea (SHK, SHO); and Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea (ARK, HSC, MYK, EHC, BYC).
Medicine (Baltimore). 2015 Oct;94(43):e1817. doi: 10.1097/MD.0000000000001817.
Unilateral sensorineural hearing loss (USNHL)/single-side deafness (SSD) is a frequently encountered disability in children. The etiology of a substantial portion of USNHL/SSD still remains unknown, and genetic causes have not been clearly elucidated. In this study, the authors evaluated the heritability of USNHL/SSD.The authors sequentially recruited 50 unrelated children with SSD. For an etiologic diagnosis, we performed a rigorous review on the phenotypes of family members of all children and conducted, if necessary, molecular genetic tests including targeted exome sequencing of 129 deafness genes.Among the 50 SSD children cohort, the authors identify 4 (8%) unrelated SSD probands from 4 families (SH136, SB173, SB177, and SB199) with another hearing impaired family members. Notably, all 4 probands in our cohort with a familial history of SSD also have pigmentary abnormalities such as brown freckles or premature gray hair within first degree relatives, which may indicate that genes whose products are involved with pigmentary disorder could be candidates for heritable SSD. Indeed, SH136 and SB199 turned out to segregate a mutation in MITF and PAX3, respectively, leading to a molecular diagnosis of Waardenburg syndrome (WS).We report, for the first time in the literature, a significant heritability of pediatric SSD. There is a strong association between the heritability of USNHL/SSD and the pigmentary abnormality, shedding a new light on the understanding of the molecular basis of heritable USNHL/SSD. In case of children with congenital SSD, it would be mandatory to rigorously screen pigmentary abnormalities. WS should also be included in the differential diagnosis of children with USNHL/SSD, especially in a familial form.
单侧感音神经性听力损失（USNHL）/单侧耳聋（SSD）是儿童中常见的残疾。相当一部分USNHL/SSD的病因仍不清楚，遗传原因也尚未明确阐明。在本研究中，作者评估了USNHL/SSD的遗传度。作者依次招募了50名无亲缘关系的SSD儿童。为了进行病因诊断，我们对所有儿童家庭成员的表型进行了严格审查，并在必要时进行了分子遗传学检测，包括对129个耳聋基因进行靶向外显子测序。在这50名SSD儿童队列中，作者从4个家庭（SH136、SB173、SB177和SB199）中识别出4名（8%）无亲缘关系的SSD先证者，这些家庭中有其他听力受损的家庭成员。值得注意的是，我们队列中所有有SSD家族史的4名先证者在一级亲属中也有色素异常，如棕色雀斑或早生白发，这可能表明其产物与色素紊乱有关的基因可能是遗传性SSD的候选基因。事实上，SH136和SB199分别发现了MITF和PAX3的突变，从而得出了瓦登伯革综合征（WS）的分子诊断。我们在文献中首次报道了小儿SSD的显著遗传度。USNHL/SSD的遗传度与色素异常之间存在密切关联，这为理解遗传性USNHL/SSD的分子基础提供了新的线索。对于先天性SSD儿童，必须严格筛查色素异常。WS也应纳入USNHL/SSD儿童的鉴别诊断中，尤其是家族性形式。
