Recker Florian, Zaniew Marcin, Böckenhauer Detlef, Miglietti Nunzia, Bökenkamp Arend, Moczulska Anna, Rogowska-Kalisz Anna, Laube Guido, Said-Conti Valerie, Kasap-Demir Belde, Niemirska Anna, Litwin Mieczysław, Siteń Grzegorz, Chrzanowska Krystyna H, Krajewska-Walasek Małgorzata, Sethi Sidharth K, Tasic Velibor, Anglani Franca, Addis Maria, Wasilewska Anna, Szczepańska Maria, Pawlaczyk Krzysztof, Sikora Przemysław, Ludwig Michael
Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Pediatr Nephrol. 2015 Jun;30(6):931-43. doi: 10.1007/s00467-014-3013-2. Epub 2014 Dec 6.
The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked multi-systemic disorder, almost always characterized by the triad of congenital cataract, cognitive and behavioral impairment and a proximal tubulopathy.
Twenty-eight novel patients with suspected Lowe syndrome were studied.
All patients carried OCRL gene defects with mutational hot spots at CpG dinucleotides. Mutations previously unknown in Lowe syndrome were observed in ten of the 28 patients, and carriership was identified in 30.4 % of the mothers investigated. Mapping the exact breakpoints of a complete OCRL gene deletion revealed involvement of several flanking repeat elements. We noted a similar pattern of documented clinically relevant symptoms, and even though the patient cohort comprised relatively young patients, 32 % of these patients already showed advanced chronic kidney disease. Thrombocytopenia was seen in several patients, and hyperosmia and/or hyperacusis were reported recurrently. A p.Asp523Asn mutation in a Polish patient, associated with the typical cerebrorenal spectrum but with late cataract (10 year), was also evident in two milder affected Italian brothers with ocular involvement of similar progression.
We have identified clinical features in 28 patients with suspected Lowe syndrome that had not been recognized in Lowe syndrome prior to our study. We also provide further evidence that OCRL mutations cause a phenotypic continuum with selective and/or time-dependent organ involvement. At least some of these mutants might exhibit a genotype-phenotype correlation.
洛氏眼脑肾综合征（OCRL）是一种罕见的X连锁多系统疾病，几乎总是以先天性白内障、认知和行为障碍以及近端肾小管病三联征为特征。
对28例疑似洛氏综合征的新患者进行了研究。
所有患者均携带OCRL基因缺陷，CpG二核苷酸处存在突变热点。在28例患者中有10例观察到此前未知的洛氏综合征突变，在30.4%接受调查的母亲中发现了携带者。绘制完整OCRL基因缺失的确切断点图谱显示，几个侧翼重复元件参与其中。我们注意到记录的临床相关症状有相似模式，尽管患者队列包括相对年轻的患者，但其中32%的患者已出现晚期慢性肾病。在几名患者中观察到血小板减少，且反复报告有嗅觉过敏和/或听觉过敏。一名波兰患者的p.Asp523Asn突变，与典型的脑肾谱系相关但白内障出现较晚（10岁），在两名病情较轻、有类似进展眼部受累的意大利兄弟中也很明显。
我们在28例疑似洛氏综合征患者中发现了本研究之前洛氏综合征未被认识的临床特征。我们还提供了进一步证据，表明OCRL突变导致具有选择性和/或时间依赖性器官受累的表型连续体。这些突变体中至少有一些可能表现出基因型与表型的相关性。
