DermKnowledgeBASE: lowe syndrome

lowe syndrome

Semantic LIterature Summary Engine (SLISE)

( SLISE(Summary) - Drag this link to bookmarks bar for instant search)

Skin Deep - A Dermatology Blog

Loading........Please wait.

The text is the summary of recent articles on lowe syndrome at 75 thresold from National Library of Medicine (NLM). This information is subject to NCBI's Disclaimer and Copyright notice.

Patients with lowe syndrome present congenital cataracts, mental disabilities and a Renal Proximal tubulopathy, whereas patients with Dent-2 disease exhibit similar Proximal tubule dysfunction but only mild, or no additional clinical defects [1]. It is not yet understood why some OCRL mutations cause the phenotype of lowe syndrome, while others develop the milder phenotype of Dent-2 disease [2]. The patient suffered from bilateral congenital cataracts and glaucoma, striking growth Deficiency, severe psychomotor disability, a severe osteopathy, and seizures, but only minimal renal dysfunction [3]. The most common ocular anomalies were congenital cataract, retinal dystrophies, glaucoma, and retinoblastoma in order of frequency [4]. A truncating Mutation in exon 8 of OCRL1 was reported in a case of Lowe syndrome with cataract [5].

Several PI 5-phosphatases have been linked to human genetic diseases, in particular the Lowe protein or OCRL which is mutated in the Lowe syndrome [6]. PI 5-phosphatases have been reported to control cell migration, adhesion, polarity and cell invasion particularly in cancer Cells [7]. The two PI 5-phosphatases SHIP2 or SKIP could be Localized at the plasma membrane and can reduce either PI(3,4,5)P3 or PI(4,5)P2 abundance [8]. Mutations in OCRL, an inositol polyphosphate 5-phosphatase that dephosphorylates PI(4,5)P2, cause lowe syndrome [9]. Accumulation of ciliary PI(4,5)P2 was pronounced in mouse embryonic fibroblasts (MEFs) derived from lowe syndrome mouse model as well as in Ocrl-null MEFs, which was reversed by reintroduction of OCRL [10].

Accumulation of sonic hedgehog protein in response to hedgehog agonist was decreased in MEFs derived from a lowe syndrome mouse model [11]. In this report, we conducted genetic testing of a patient clinically diagnosed with lowe syndrome to detect the presence of OCRL variants [12]. We analyzed variant transcript expression in peripheral blood leukocytes and using a minigene construct in addition to in silico analysis [13]. Among the 126 cases, 79 were identified as microdeletion/microduplication syndromes, which included 15q24 microdeletion syndrome, Xq28 microduplication syndrome, and lowe syndrome [14]. OCRL1 encodes an inositol polyphosphate 5-phosphatase which preferentially dephosphorylates phosphatidylinositide 4,5 bisphosphate (PI(4,5)P2) [15].

We have identified two novel Mutations in two unrelated Lowe syndrome patients with congenital glaucoma [16]. There are a handful of reports of pubertal delay, infertility and cryptorchidism in lowe syndrome [17]. The constellation of further abnormalities suggested Lowe syndrome: hypotonia, bilateral cataracts (surgical extraction and intraocular lens implantation) and renal tubular acidosis (microscopic haematuria, hypercalciuria, proteinuria, generalised aminoaciduria, hypophosphataemia and metabolic acidosis) [18]. Common dysmorphic oculofacial findings include anophthalmia, microphthalmia, hypertelorism, and abnormalities in the configuration or orientation of the palpebral Fissures [19]. Nearly 200 OCRL mutations related to lowe syndrome have been found worldwide, with only ten mutations among the Chinese population [20].

Mutations in this gene cause lowe syndrome (LS) or type 2 Dent disease, of which low-molecular-weight (LMW) proteinuria is a characteristic feature [21]. Genetic factors have been shown to play an important role in the pathogenesis of congenital cataract [22]. The current genetic models of congenital cataract include Autosomal Dominant, Autosomal recessive, and sex-linked Inheritance [23]. Sex-linked congenital cataract could be inherited through the X or Y chromosome [24]. Congenital cataract is a Symptom associated with several X-linked disorders, including Nance-Horan syndrome, Lowe syndrome, Conradi-H√ľnermann-Happle syndrome, oculo-facio-cardio-dental syndrome, and Alport syndrome [25].

On the other Hand, the mechanism and characteristics of Y-linked congenital cataract remains to be identified [26]. Despite its rarity, sex-linked congenital cataract has been known to seriously affect the quality of life of patients [27]. In this review, we present our current understanding of the genes and loci associated with sex-linked congenital cataract [28]. OCRL variants have not only been found in classic lowe syndrome, but also in patients with a predominantly Renal phenotype classified as Dent disease type 2 (Dent-2) [29]. Recent data indicate that there is a phenotypic continuum between Dent-2 disease and Lowe syndrome, suggesting that there are Individual differences in the ability to compensate for the loss of enzyme function [30].

To address this, we determined the glomerular sieving coefficient of renin and prorenin and measured urinary renin/prorenin 1) after inducing prorenin in Cyp1a1-Ren2 rats and 2) in patients with Dent disease or Lowe syndrome, disorders characterized by defective Proximal tubular reabsorption [31]. They are 10 different isoenzymes and several splice variants in the human genome that are involved in a series of human pathologies such as the lowe syndrome, the Joubert and MORM syndromes, breast cancer, glioblastoma, gastric cancer and several other type of cancers [32]. Inositol 5-phosphatases can be amplified in human cancer Cells, whereas the 3- and 4- phosphatase Tumor suppressor PTEN and INPP4B, repectively are often repressed or deleted [33]. The inositol 5-phosphatases are critically involved in a complex network of higly regulated phosphoinositides, affecting the lipid content of PI(3, 4, 5)P3, PI(4, 5)P2 and PI(3, 4)P2 [34]. OCRL1 5-phosphatase activity, which is membrane curvature sensitive, is stimulated by IPIP27A-mediated engagement of OCRL1 with pacsin 2 and promotes scission of MPR-containing carriers [35].

This lack of homogeneity of clinical manifestations suggests that the difference in phenotypes between the two groups might reflect different pathophysiological mechanisms, probably depending on the diverse genes involved [36]. In particular in vitro and in vivo evidence demonstrates an important role of OCRL in recycling of megalin, a multi-ligand receptor crucial for reabsorption of nutrients in the proximal tubulus, a process severely impaired in lowe syndrome patients [37]. These results indicate for the first time that OCRL1 is required for endocytic trafficking in vivo, and strongly support the hypothesis that endocytic defects are responsible for the renal tubulopathy in lowe syndrome and Dent-2 disease [38]. Clinical and laboratory findings of lowe syndrome are well documented [39]. To search for mechanisms linked to clinical variability observed between these two OCRL mutation-associated pathologies, we compared Dermal fibroblasts from independent patients, four affected by Dent-2 disease and six with lowe syndrome [40].

References: 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ,

Press Refresh to fetch fresh content with references from pubmed. This content was cached on

comments powered by Disqus


This is an experimental application for healthcare professionals. The information presented here is not intended to diagnose, treat, cure or prevent any disease. Read disclaimer. - Evidence based skincare free

About Me

I have varied research interests ranging from eHealth, Health Information Exchange, Clinical Trials and Research, Contact Dermatitis, Bioinformatics, and Cosmetic Dermatology. I have work experience in Canada as an eHealth analyst, and in Dubai and India as a Specialist Dermatologist.


Bell Raj Eapen
Hamilton, ON