Cho Hee Yeon, Lee Bum Hee, Choi Hyun Jin, Ha Il Soo, Choi Yong, Cheong Hae Il
Department of Pediatrics, Gachon University of Medicine and Science, Gil Medical Center, Incheon, South Korea.
Pediatr Nephrol. 2008 Feb;23(2):243-9. doi: 10.1007/s00467-007-0686-9. Epub 2007 Nov 24.
To date, two responsible genes for the development of Dent disease have been identified: CLCN5 and OCRL1. In this study, genotype-phenotype correlations were studied in patients with Dent disease and those with Lowe syndrome. Among the 12 boys with a phenotype typical of Dent disease, nine had a mutation in CLCN5 (Dent disease 1), two had a mutation in OCRL1 (Dent disease 2), and one had no mutations in either gene. All seven boys with a clinical diagnosis of Lowe syndrome had a mutation in OCRL1. Patients with Lowe syndrome showed more frequent hypophosphatemia/rickets and more prominent tubular proteinuria than patients with Dent disease 1, and patients with Dent disease 2 had higher degree of tubular proteinuria and hypercalciuria than patients with Dent disease 1. Additionally, one patient with Dent disease 2 showed a mild degree of developmental delay, elevated serum muscle enzyme levels, and cryptorchidism. In this study, the genetic heterogeneity in Dent disease and the phenotypic heterogeneity in Lowe syndrome were confirmed. In patients with Dent disease, the presence of the above-mentioned extrarenal manifestations indicates that it is more likely that the patient is affected by Dent disease 2 than by Dent disease 1.
迄今为止，已鉴定出两种与丹特病（Dent disease）发生相关的基因：CLCN5和OCRL1。在本研究中，对丹特病患者和 Lowe 综合征患者进行了基因型-表型相关性研究。在 12 名具有典型丹特病表型的男孩中，9 名在CLCN5基因发生突变（丹特病 1 型），2 名在OCRL1基因发生突变（丹特病 2 型），1 名在这两个基因中均未发生突变。所有 7 名临床诊断为 Lowe 综合征的男孩在OCRL1基因均有突变。与丹特病 1 型患者相比，Lowe 综合征患者低磷血症/佝偻病更为常见，肾小管蛋白尿更为突出；与丹特病 1 型患者相比，丹特病 2 型患者肾小管蛋白尿和高钙尿症程度更高。此外，1 名丹特病 2 型患者表现出轻度发育迟缓、血清肌肉酶水平升高和隐睾症。在本研究中，证实了丹特病的基因异质性和 Lowe 综合征的表型异质性。在丹特病患者中，上述肾外表现的存在表明该患者受丹特病 2 型影响的可能性大于丹特病 1 型。
