Abstract：
OBJECTIVE: To report genetic and clinical findings in a case series of 10 patients from eight unrelated families diagnosed with Senior-Løken syndrome.
METHODS: A retrospective study of patients with Senior-Løken syndrome. Data collected included clinical findings electroretinography and ocular imaging. Genetic analysis was based on molecular inversion probes, whole-exome sequencing (WES), and Sanger sequencing.
RESULTS: All patients who underwent electrophysiology (8/10) had widespread photoreceptor degeneration. Genetic analysis revealed two mutations in NPHP1, two mutations in NPHP4, and two mutations in IQCB1 (NPHP5). Five of the six mutations identified in the current study were found in a single family each in our cohort. The IQCB1-p.R461* mutation has been identified in 3 families. Patients harboring mutations in IQCB1 were diagnosed with Leber congenital amaurosis, while patients with NPHP4 and NPHP1 mutations showed early and sector retinitis pigmentosa, respectively. Full-field electroretinography was extinct for 6 of 10 patients, moderately decreased for two, and unavailable for another 2 subjects. Renal involvement was evident in 7/10 patients at the time of diagnosis. Kidney function was normal (based on serum creatinine) in patients younger than 10 years. Mutations in IQCB1 were associated with high hypermetropia, whereas mutations in NPHP4 were associated with high myopia.
CONCLUSIONS: Patients presenting with infantile inherited retinal degeneration are not universally screened for renal dysfunction. Modern genetic tests can provide molecular diagnosis at an early age and therefore facilitate early diagnosis of renal disease with recommended periodic screening beyond childhood and family planning.
METHODS: A retrospective study of patients with Senior-Løken syndrome. Data collected included clinical findings electroretinography and ocular imaging. Genetic analysis was based on molecular inversion probes, whole-exome sequencing (WES), and Sanger sequencing.
RESULTS: All patients who underwent electrophysiology (8/10) had widespread photoreceptor degeneration. Genetic analysis revealed two mutations in NPHP1, two mutations in NPHP4, and two mutations in IQCB1 (NPHP5). Five of the six mutations identified in the current study were found in a single family each in our cohort. The IQCB1-p.R461* mutation has been identified in 3 families. Patients harboring mutations in IQCB1 were diagnosed with Leber congenital amaurosis, while patients with NPHP4 and NPHP1 mutations showed early and sector retinitis pigmentosa, respectively. Full-field electroretinography was extinct for 6 of 10 patients, moderately decreased for two, and unavailable for another 2 subjects. Renal involvement was evident in 7/10 patients at the time of diagnosis. Kidney function was normal (based on serum creatinine) in patients younger than 10 years. Mutations in IQCB1 were associated with high hypermetropia, whereas mutations in NPHP4 were associated with high myopia.
CONCLUSIONS: Patients presenting with infantile inherited retinal degeneration are not universally screened for renal dysfunction. Modern genetic tests can provide molecular diagnosis at an early age and therefore facilitate early diagnosis of renal disease with recommended periodic screening beyond childhood and family planning.
摘要：
目的：报告来自8个不相关家庭的10名患者的遗传和临床发现。
方法：对老年-Løken综合征患者的回顾性研究。收集的数据包括临床发现视网膜电图和眼部成像。遗传分析基于分子倒置探针，全外显子组测序（WES），还有Sanger测序.
结果：所有接受电生理学（8/10）的患者都有广泛的光感受器变性。遗传分析显示NPHP1有两个突变，NPHP4有两个突变，IQCB1有两个突变（NPHP5）。在本研究中确定的六个突变中的五个在我们的队列中的一个家庭中发现。IQCB1-p。已在3个家族中鉴定出R461*突变。IQCB1突变的患者被诊断为Leber先天性黑蒙，而NPHP4和NPHP1突变的患者显示早期和部门性视网膜色素变性，分别。10名患者中有6名已经绝迹了全视野视网膜电描记术,适度减少两个，和不可用于另外两个科目。在诊断时，有7/10的患者肾脏受累明显。10岁以下患者的肾功能正常（基于血清肌酐）。IQCB1的突变与高度远视有关，而NPHP4突变与高度近视相关.
结论：患有婴儿遗传性视网膜变性的患者没有普遍筛查肾功能障碍。现代基因检测可以在早期提供分子诊断，因此有助于肾脏疾病的早期诊断，建议在儿童和计划生育之后进行定期筛查。
方法：对老年-Løken综合征患者的回顾性研究。收集的数据包括临床发现视网膜电图和眼部成像。遗传分析基于分子倒置探针，全外显子组测序（WES），还有Sanger测序.
结果：所有接受电生理学（8/10）的患者都有广泛的光感受器变性。遗传分析显示NPHP1有两个突变，NPHP4有两个突变，IQCB1有两个突变（NPHP5）。在本研究中确定的六个突变中的五个在我们的队列中的一个家庭中发现。IQCB1-p。已在3个家族中鉴定出R461*突变。IQCB1突变的患者被诊断为Leber先天性黑蒙，而NPHP4和NPHP1突变的患者显示早期和部门性视网膜色素变性，分别。10名患者中有6名已经绝迹了全视野视网膜电描记术,适度减少两个，和不可用于另外两个科目。在诊断时，有7/10的患者肾脏受累明显。10岁以下患者的肾功能正常（基于血清肌酐）。IQCB1的突变与高度远视有关，而NPHP4突变与高度近视相关.
结论：患有婴儿遗传性视网膜变性的患者没有普遍筛查肾功能障碍。现代基因检测可以在早期提供分子诊断，因此有助于肾脏疾病的早期诊断，建议在儿童和计划生育之后进行定期筛查。
