PDF(Pubmed)
Abstract：
Dent disease is a rare X-linked renal tubulopathy due to CLCN5 and OCRL (DD2) mutations. OCRL mutations also cause Lowe syndrome (LS) involving the eyes, brain and kidney. DD2 is frequently described as a mild form of LS because some patients may present with extra-renal symptoms (ESs). Since DD2 is a rare disease and there are a low number of reported cases, it is still unclear whether it has a clinical picture distinct from LS. We retrospectively analyzed the phenotype and genotype of our cohort of 35 DD2 males and reviewed all published DD2 cases. We analyzed the distribution of mutations along the OCRL gene and evaluated the type and frequency of ES according to the type of mutation and localization in OCRL protein domains. The frequency of patients with at least one ES was 39%. Muscle findings are the most common ES (52%), while ocular findings are less common (11%). Analysis of the distribution of mutations revealed (1) truncating mutations map in the PH and linker domain, while missense mutations map in the 5-phosphatase domain, and only occasionally in the ASH-RhoGAP module; (2) five OCRL mutations cause both DD2 and LS phenotypes; (3) codon 318 is a DD2 mutational hot spot; (4) a correlation was found between the presence of ES and the position of the mutations along OCRL domains. DD2 is distinct from LS. The mutation site and the mutation type largely determine the DD2 phenotype.
摘要：
由于CLCN5和OCRL（DD2）突变，Dent病是一种罕见的X连锁肾小管病。OCRL突变也会导致Lowe综合征（LS）累及眼睛，大脑和肾脏.DD2通常被描述为轻度形式的LS，因为一些患者可能存在肾外症状（ESs）。由于DD2是一种罕见疾病，报告病例数较少，目前尚不清楚它是否具有与LS不同的临床表现.我们回顾性分析了35名DD2男性的表型和基因型，并回顾了所有已发表的DD2病例。我们分析了OCRL基因突变的分布，并根据OCRL蛋白结构域中的突变类型和定位评估了ES的类型和频率。患有至少一种ES的患者的频率为39％。肌肉的发现是最常见的ES（52％），而眼部表现较少见（11%）。对突变分布的分析揭示了（1）PH和接头结构域中的截短突变图，而错义突变位于5-磷酸酶结构域，并且仅偶尔在ASH-RhoGAP模块中；（2）五个OCRL突变同时引起DD2和LS表型；（3）密码子318是DD2突变热点；（4）在ES的存在与OCRL结构域上的突变位置之间发现了相关性。DD2不同于LS。突变位点和突变类型在很大程度上决定了DD2表型。
