PDF(Pubmed)
Abstract：
Norrie disease (ND; OMIM 310600), a rare X-linked recessive genetic disorder, is characterized by congenital blindness and occasionally, sensorineural hearing loss, and developmental delay. The congenital blindness of ND patients is almost untreatable; thus, hearing is particularly important for them. However, the mechanism of hearing loss of ND patients is unclear, and no good treatment is available except wearing hearing-aid. Therefore, revealing the mechanism of hearing loss in ND patients and exploring effective treatment methods are greatly important. In addition, as a serious monogenic genetic disease, convenient gene identification method is important for ND patients and their family members, as well as prenatal diagnosis and preimplantation genetic diagnosis to block intergenerational transmission of pathogenic genes. In this study, a Norrie family with two male patients was reported. This pedigree was ND caused by large fragment deletion of NDP (norrin cystine knot growth factor NDP) gene. In addition to typical severe ophthalmologic and audiologic defects, the patients showed new pathological features of endolymphatic hydrops (EH), and they also showed acoustic nerves abnormal as described in a very recent report. PCR methods were developed to analyze and diagnose the variation of the family members. This study expands the understanding of the clinical manifestation and pathogenesis of ND and provides a new idea for the treatment of patients in this family and a convenient method for the genetic screen for this ND family.
摘要：
诺里病（ND；OMIM310600），一种罕见的X连锁隐性遗传病,以先天性失明为特征，偶尔，感觉神经性听力损失,和发育迟缓。ND患者的先天性失明几乎是无法治愈的；因此，听力对他们来说尤其重要。然而,ND患者听力损失的机制尚不清楚，除了戴助听器，没有好的治疗方法。因此,揭示ND患者听力损失的机制,探索有效的治疗方法具有重要意义。此外,作为一种严重的单基因遗传病，方便的基因鉴定方法对于ND患者及其家庭成员,以及产前诊断和植入前遗传学诊断，以阻断致病基因的代际传播。在这项研究中,据报道，诺里一家有两名男性患者。该家系是由NDP（norrin胱氨酸结生长因子NDP）基因的大片段缺失引起的ND。除了典型的严重眼科和听力学缺陷，患者出现新的内淋巴水肿（EH）病理特征，如最近的一份报告所述，他们还显示出听觉神经异常。开发了PCR方法来分析和诊断家族成员的变异。本研究拓展了对ND的临床表现和发病机制的认识，为该家族患者的治疗提供了新的思路，为该ND家族的遗传筛查提供了一种便捷的方法。
