Department of Surgical Sciences, Eye Clinic, Università degli Studi di Torino, Torino, 10122, Italy.
Low vision Unit, Ospedale Oftalmico Sperino Torino, Torino, 10122, Italy.
Sci Rep. 2017 Nov 15;7(1):15681. doi: 10.1038/s41598-017-16014-z.
We report results of DNA analysis with next generation sequencing (NGS) of 21 consecutive Italian patients from 17 unrelated families with clinical diagnosis of Usher syndrome (4 USH1 and 17 USH2) searching for mutations in 11 genes: MYO7A, CDH23, PCDH15, USH1C, USH1G, USH2A, ADGVR1, DFNB31, CLRN1, PDZD7, HARS. Likely causative mutations were found in all patients: 25 pathogenic variants, 18 previously reported and 7 novel, were identified in three genes (USH2A, MYO7A, ADGRV1). All USH1 presented biallelic MYO7A mutations, one USH2 exhibited ADGRV1 mutations, whereas 16 USH2 displayed USH2A mutations. USH1 patients experienced hearing problems very early in life, followed by visual impairment at 1, 4 and 6 years. Visual symptoms were noticed at age 20 in a patient with homozygous novel MYO7A missense mutation c.849G > A. USH2 patients' auditory symptoms, instead, arose between 11 months and 14 years, while visual impairment occurred later on. A homozygous c.5933_5940del;5950_5960dup in USH2A was detected in one patient with early deafness. One patient with homozygous deletion from exon 23 to 32 in USH2A suffered early visual symptoms. Therefore, the type of mutation in USH2A and MYO7A genes seems to affect the age at which both auditory and visual impairment occur in patients with USH.
我们报告了对 21 名连续的意大利患者进行 DNA 分析的结果，这些患者来自 17 个无关家庭，临床诊断为 Usher 综合征（4 名 USH1 和 17 名 USH2），目的是在 11 个基因中寻找突变：MYO7A、CDH23、PCDH15、USH1C、USH1G、USH2A、ADGVR1、DFNB31、CLRN1、PDZD7、HARS。在所有患者中均发现了可能的致病突变：在三个基因（USH2A、MYO7A、ADGRV1）中鉴定出 25 种致病性变异，其中 18 种是先前报道的，7 种是新的。所有 USH1 均表现为双等位基因 MYO7A 突变，1 名 USH2 表现为 ADGRV1 突变，而 16 名 USH2 表现为 USH2A 突变。USH1 患者在生命早期就出现听力问题，随后在 1、4 和 6 岁时出现视力障碍。一名纯合新型 MYO7A 错义突变 c.849G>A 的患者在 20 岁时出现视觉症状。相反，USH2 患者的听觉症状出现在 11 个月至 14 岁之间，而视力障碍则出现在稍后。一名 USH2A 患者携带纯合 c.5933_5940del;5950_5960dup 突变，该患者耳聋较早。一名 USH2A 患者exon23 到 32 缺失，表现为早期视觉症状。因此，USH2A 和 MYO7A 基因突变的类型似乎会影响 USH 患者听觉和视觉障碍发生的年龄。
