Dent disease type 2

General Information (adopted from Orphanet):

Synonyms, Signs: Nephrolithiasis type 2, Dent disease 2
Number of Symptoms 25
OrphanetNr: 93623
OMIM Id: 300555
ICD-10: N25.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 28 cases
Inheritance:
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Dent disease
 -Rare genetic disease
 -Rare renal disease

Comment:

OCRL1 mutations also cause the oculocerebrorenal syndrome of Lowe. Analysis of all known OCRL1 mutations show that Dent 2 mutations fall into two classes that do not overlap with Lowe mutations (PMID:19390221). Of the 32 families with the clinical diagnosis of Dent–Wrong disease, 19 had mutations in CLCN5 (Dent disease 1) and 5 had mutations in OCRL1 (Dent disease 2), but the diagnosis of Lowe syndrome had been excluded in the members of the latter families because cataracts were absent. A subset of patients with Dent–Wrong disease do not have any mutations in either of the above genes (PMID:25852908). Mild peripheral cataract has been described in 2 of 28 patients with DENT-2 (PMID:19559295). OCRL1 mutations associated with Dent disease 2 do not overlap with those causing Lowe syndrome. All of the OCRL1 missense mutations associated with Dent's disease occur in the 5' region of the gene (exons 4 to 15) and involve the phosphatidylinositol phosphate 5-phosphatase domain of the OCRL1 protein, whilst the truncating mutations are in the first seven exons or intron 7. The OCRL1 mutations that are found in Lowe syndrome patients occur primarily in exons 9-22, which encode the 3 large functional domains (PMID:20946626).

Symptom Information: Sort by abundance 

1
 (HPO:0000083) Renal insufficiency Occasional [IBIS] 32% (n=25) 19559295 IBIS 232 / 7739
2
 (HPO:0002150) Hypercalciuria Very frequent [IBIS] 86% (n=28) 19559295 IBIS 45 / 7739
3
 (HPO:0003355) Aminoaciduria Frequent [IBIS] 52% (n=21) 19559295 IBIS 65 / 7739
4
 (HPO:0001947) Renal tubular acidosis 4% (n=27) 19559295 IBIS 21 / 7739
5
 (HPO:0002907) Microscopic hematuria 2/6 19390221 IBIS 27 / 7739
6
 (HPO:0003076) Glycosuria Occasional [IBIS] 11% (n=28) 19559295 IBIS 32 / 7739
7
 (HPO:0012622) Chronic kidney disease 25852908 IBIS 32 / 7739
8
 (HPO:0012213) Decreased glomerular filtration rate Very frequent [IBIS] 3/3 19390221 IBIS 21 / 7739
9
 (HPO:0003126) Low-molecular-weight proteinuria Very frequent [IBIS] 100% (n=28) 19559295 IBIS 7 / 7739
10
 (HPO:0000121) Nephrocalcinosis 39% (n=28) 19559295 IBIS 57 / 7739
11
 (HPO:0000114) Proximal tubulopathy 25852908 IBIS 18 / 7739
12
 (HPO:0000518) Cataract occasional [IBIS] 2/28 19559295 IBIS 454 / 7739
13
 (HPO:0001263) Global developmental delay 19559295 IBIS 853 / 7739
14
 (HPO:0100543) Cognitive impairment 19559295 IBIS 230 / 7739
15
 (HPO:0001249) Intellectual disability 20946626 IBIS 1089 / 7739
16
 (HPO:0002748) Rickets Frequent [IBIS] 3/6 19390221 IBIS 41 / 7739
17
 (HPO:0004322) Short stature 19559295 IBIS 1232 / 7739
18
 (HPO:0002900) Hypokalemia 6% (n=18) 19559295 IBIS 45 / 7739
19
 (HPO:0003236) Elevated serum creatine phosphokinase 24912603 IBIS 214 / 7739
20
 (HPO:0002148) Hypophosphatemia Occasional [IBIS] 24% (n=25) 19559295 IBIS 43 / 7739
21
 (HPO:0009004) Hypoplasia of the musculature occasional [IBIS] 1/5 24912603 IBIS 7 / 7739
22
 (HPO:0001252) Muscular hypotonia 1/6 19390221 IBIS 990 / 7739
23
 (MedDRA:10003481) Aspartate aminotransferase increased 24912603 IBIS 4 / 7739
24
 (OMIM) Increased lactate dehydrogenase 24912603 IBIS 2 / 7739
25
 (OMIM) Developmental delay, mild 19390221; 24912603 IBIS 8 / 7739

Associated genes:

OCRL;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Hoopes et al. (2005) reported 5 families with Dent disease with mutations in the OCRL1 gene. PIP(2) 5-phosphatase activity was markedly reduced in skin fibroblasts cultured from the probands, and protein expression, measured by Western blot analysis, was ...
Molecular genetics OMIM Hoopes et al. (2005) reported affected members of 13 families with Dent disease in whom mutations in the CLCN5 gene (300008) were excluded, indicating genetic heterogeneity. In 5 of these 13 families, they identified mutations in the OCRL ...