Glomerulocystic Kidney Disease Research Articles

Glomerulocystic Kidney Disease with Concurrent Thin Basement Membrane Disease in an Adult Male

Glomerulocystic Kidney Disease with Concurrent Thin Basement Membrane Disease in an Adult Male

Hepatocyte nuclear factors play an important role in the pathogenesis of nephropathy

Hepatocyte nuclear factors play an important role in the pathogenesis of nephropathy

Hepatocyte Nuclear Factor 1 Beta Mutation-associated Newborn Onset of Glomerulocystic Kidney Disease: A Case Presentation.

Mutations in hepatocyte nuclear factor-1 beta (HNF1B) are the most commonly identified genetic cause of renal malformations. Heterozygous mutations are associated with renal cysts and diabetes syndrome. Various renal developmental abnormalities and maturity-onset diabetes of the young could be the presenting factors of these mutations. A 10-year-old boy who was evaluated for bilateral cystic kidneys and chronic kidney disease from the newborn period was diagnosed with HNF1B-related glomerulocystic disease by DNA sequencing. The differential diagnosis of autosomal dominant polycystic kidney disease was a diagnostic pitfall. The genetic screening of the family revealed his mother, sister, and brother to have the same mutation. Therefore, genetic diagnosis and counseling are important for cystic kidney diseases not only for formulating the diagnosis and early management plan but also for the diagnosis of potential asymptomatic cases in the family.

A case of digenic maturity onset diabetes of the young with heterozygous variants in both HNF1Α and HNF1Β genes

BackgroundMaturity onset diabetes of the young (MODY) is the most commonly reported form of monogenic diabetes in the pediatric population. Only a few cases of digenic MODY have been reported up to now. Case reportA female patient was diagnosed with diabetes at the age of 7 years and was treated with insulin. A strong family history of diabetes was present in the maternal side of the family. The patient also presented hypomagnesemia, glomerulocystic kidney disease and a bicornuate uterus. Genetic testing of the patient revealed that she was a double heterozygous carrier of HNF1A gene variant c.685C > T; (p.Arg229Ter) and a whole gene deletion of the HNF1B gene. Her mother was a carrier of the same HNF1A variant. ConclusionDigenic inheritance of MODY pathogenic variants is probably more common than currently reported in literature. The use of Next Generation Sequencing panels in testing strategies for MODY could unmask such cases that would otherwise remain undiagnosed.

Renal oligohydramnios and Potter sequence with cystic kidney disease

For the first time in 1946 E.L. Potter (1901–1993) described the characteristic appearance of stillborns and deceased newborns with bilateral renal agenesis. Due to the further observations Potter distinguished the syndrome (Q60.6) – a set of characteristic external signs that are formed due to the extreme degree of oligohydramnios and intrauterine compression of the fetus. Classical Potter syndrome is diagnosed by the disfunction of both kidneys in the fetus (for example, bilateral agenesis), which leads to death. The term «Potter sequence» or oligohydramnios sequence with diverse causes has received the wide clinical use. The term «renal oligohydramnios» (ROH) is used to describe oligohydramnios resulting from a decrease or absence of fetal kidney function. The authors state that renal oligohydramnios and Potter sequence often develop in the fetus with cystic kidney disease with the formation of cysts in the parenchyma of both kidneys (autosomal recessive polycystic kidney disease, autosomal dominant polycystic kidney disease, glomerulocystic kidney disease associated with HNF1ß/TCF2 gene mutations, renal-coloboma syndrome, cystic renal hypoplasia, cystic renal dysplasia with mutations of the CEP55 gene).

Clinical and genetic features of glomerulocystic kidney in childhood

The review provides historical information on the study of renal cystosis that occurs with glomerular cysts, discusses terminology issues and classification of diseases that occur with glomerulocystic kidney. The course features, diagnostic methods, treatment, and prognosis of renal glomerulocystosis in children, renal and extrarenal manifestations of two subtypes of hereditary glomerulocystic kidney disease: autosomal dominant glomerulocystic kidney disease associated with mutations of uromodulin (OMIM 609886) and familial hypoplastic glomerulocystic kidney disease associated with mutations of the HNF-1β (TCF2) gene (OMIM 137920). Diagnostic tetrad of familial hypoplastic glomerulocystic kidney disease, features of course and prognosis of HNF-1β-associated kidney disease with very early onset (VEO), MODY5 diabetes caused by HNF-1β mutation and 17q12 microdeletion syndrome in children were detected. According to the results of ultrasound examination (US), the fetus and newborn reveal hyperechogenicity of the kidney parenchyma, the volume of which is increased or corresponds to normal values. Renal cysts in glomerulocystic kidney are small, located in the cortical layer or subcapsularly, single or multiple, rarely diagnosed in the neonatal period. In young children, US shows a picture of increasing hyperechogenicity of the parenchyma with visualization of renal cysts in the cortical layer or subcapsularly, a decrease in the volume or asymmetry in the size of the kidneys. Urinary syndrome in glomerulocystic kidney in childhood is characterized by hematuria, microproteinuria, magniuria and uraturia in combination with hypostenuria and polyuria. Molecular genetic research reveals the mutation of genes responsible for the development of inherited diseases that occur with glomerulocystic kidney, and largely determines the prognosis and management tactics of the patient. A systematic approach is needed in the diagnosis and treatment of glomerulocystic kidney in children in order to slow the progression of chronic kidney disease and extrarenal manifestations, and to maintain continuity of observation of patients in pediatric and adult nephrological structures.

A case report of thin basement membrane nephropathy accompanied by sporadic glomerulocystic kidney disease

BackgroundThin basement membrane nephropathy (TBMN) is a relatively common disease. Patients typically present with isolated hematuria, which has a good renal prognosis. In contrast, glomerulocystic kidney disease (GCKD) is a rare disease, associated with slow progressive renal dysfunction. To our knowledge, co-occurring diagnosis of TBMN with GCKD has not been reported previously.Case presentationA 30-year old woman was admitted to our hospital for evaluation of hematuria and renal insufficiency. Upon examination, her urinary protein level was 40 mg/day and occult blood in her urine was 2+. The patient’s urinary dysmorphic red blood cell sediment was 30–49/high power field. In contrast, her serum creatinine levels increased from 0.57 mg/dl to 0.86 mg/dl during the previous 2-years, without special events. She suffered from far-sightedness and astigmatism beginning at birth; She had no family history of renal disease. Renal biopsy demonstrated cystic dilatation of the Bowman’s capsule and atrophy of the glomerular tuft. The glomerular basement membrane (GBM) was thin, with an average thickness of 191 nm. Next-generation sequencing was used to evaluate for mutations in COL4A3 and COL4A4, associated with TBMN, and UMOD, MUC1, and SEC61A1, associated with hereditary GCKD. No pathogenic mutations were identified. We thus diagnosed the patient with TBMN coexistent with sporadic GCKD.ConclusionWe report the patient diagnosed with TBMN accompanied by sporadic GCKD, based on renal biopsy and genetic testing. Because it is possible that other diseases, such as GCKD, can coexist with TBMN, it is important to consider renal biopsy.

Cystic kidney disease in children

Both the incidence and prevalence of chronic kidney disease are rising rapidly all over the world, which brings heavy economic and mental burden to the patients and the society.A retrospective study of the European Renal Association-European Dialysis and Transplant Association(ERA-EDTA) Registry showed cystic kidney disease was one of the three most prevalent rare diseases leading to renal replacement therapy before the age of 20 years.Renal cystic disease encompasses a variety of diseases that cause single or multiple cysts in the kidneys, and can be divided into 3 categories: cystic kidney disease due to fetal renal malformations, hereditary cystic kidney diseases and acquired cystic kidney diseases.Acquired renal cysts rarely occur in the general pediatric population.Renal cystic disease can present during fetus, infancy, childhood or adulthood.The onset of the disease is occult, and the clinical manifestations are heterogeneous.The manifestations may be confined to the kidney or as part of a syndrome.On renal imaging, the kidney size is normal, enlarged or small, and cysts can involve unilateral or bilateral kidneys.Family history investigation should be performed when collecting first-hand clinical data.Genetic testing can confirm the diagnosis of hereditary renal cystic disease.Cystic kidney disease is currently treated symptomatically, and patients with end-stage renal disease require renal replacement therapy. Key words: Child; Cystic kidney disease; Multicystic dysplastic kidney; Polycystic kidney disease; Glomerulocystic kidney disease

New insights into the role of HNF-1β in kidney (patho)physiology

Hepatocyte nuclear factor-1β (HNF-1β) is an essential transcription factor that regulates the development and function of epithelia in the kidney, liver, pancreas, and genitourinary tract. Humans who carry HNF1B mutations develop heterogeneous renal abnormalities, including multicystic dysplastic kidneys, glomerulocystic kidney disease, renal agenesis, renal hypoplasia, and renal interstitial fibrosis. In the embryonic kidney, HNF-1β is required for ureteric bud branching, initiation of nephrogenesis, and nephron segmentation. Ablation of mouse Hnf1b in nephron progenitors causes defective tubulogenesis, whereas later inactivation in elongating tubules leads to cyst formation due to downregulation of cystic disease genes, including Umod, Pkhd1, and Pkd2. In the adult kidney, HNF-1β controls the expression of genes required for intrarenal metabolism and solute transport by tubular epithelial cells. Tubular abnormalities observed in HNF-1β nephropathy include hyperuricemia with or without gout, hypokalemia, hypomagnesemia, and polyuria. Recent studies have identified novel post-transcriptional and post-translational regulatory mechanisms that control HNF-1β expression and activity, including the miRNA cluster miR17 ∼ 92 and the interacting proteins PCBD1 and zyxin. Further understanding of the molecular mechanisms upstream and downstream of HNF-1β may lead to the development of new therapeutic approaches in cystic kidney disease and other HNF1B-related renal diseases.

Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic disease

Primary glomerulocystic kidney disease is a special form ofrenal cystic disorder characterized by Bowman's space dilatation in the absence of tubular cysts. ZEB2 is a SMAD-interacting transcription factor involved in Mowat-Wilson syndrome, a congenital disorder with an increased risk for kidney anomalies. Here we show that deletion of Zeb2 in mesenchyme-derived nephrons with either Pax2-cre or Six2-cre causes primary glomerulocystic kidney disease without tubular cysts in mice. Glomerulotubular junction analysis revealed many atubular glomeruli in the kidneys ofZeb2 knockout mice, which explains the presence of glomerular cysts in the absence of tubular dilatation. Gene expression analysis showed decreased expression of early proximal tubular markers in the kidneys of Zeb2 knockout mice preceding glomerular cyst formation, suggesting thatdefects in proximal tubule development during early nephrogenesis contribute to the formation of congenital atubular glomeruli. At the molecular level, Zeb2 deletion caused aberrant expression of Pkd1, Hnf1β, and Glis3, threegenes causing glomerular cysts. Thus, Zeb2 regulates the morphogenesis of mesenchyme-derived nephrons andis required for proximal tubule development and glomerulotubular junction formation. Our findings also suggest that ZEB2 might be a novel disease gene in patients with primary glomerular cystic disease.

A Point Mutation in p190A RhoGAP Affects Ciliogenesis and Leads to Glomerulocystic Kidney Defects.

Rho family GTPases act as molecular switches regulating actin cytoskeleton dynamics. Attenuation of their signaling capacity is provided by GTPase-activating proteins (GAPs), including p190A, that promote the intrinsic GTPase activity of Rho proteins. In the current study we have performed a small-scale ENU mutagenesis screen and identified a novel loss of function allele of the p190A gene Arhgap35, which introduces a Leu1396 to Gln substitution in the GAP domain. This results in decreased GAP activity for the prototypical Rho-family members, RhoA and Rac1, likely due to disrupted ordering of the Rho binding surface. Consequently, Arhgap35-deficient animals exhibit hypoplastic and glomerulocystic kidneys. Investigation into the cystic phenotype shows that p190A is required for appropriate primary cilium formation in renal nephrons. P190A specifically localizes to the base of the cilia to permit axoneme elongation, which requires a functional GAP domain. Pharmacological manipulations further reveal that inhibition of either Rho kinase (ROCK) or F-actin polymerization is able to rescue the ciliogenesis defects observed upon loss of p190A activity. We propose a model in which p190A acts as a modulator of Rho GTPases in a localized area around the cilia to permit the dynamic actin rearrangement required for cilia elongation. Together, our results establish an unexpected link between Rho GTPase regulation, ciliogenesis and glomerulocystic kidney disease.

CT and MR imaging for evaluation of cystic renal lesions and diseases.

Cystic renal lesions are commonly encountered in abdominal imaging. Although most cystic renal lesions are benign simple cysts, complex renal cysts, infectious cystic renal disease, and multifocal cystic renal disease are also common phenomena. The Bosniak classification system provides a useful means of categorizing cystic renal lesions but places less emphasis on their underlying pathophysiology. Cystic renal diseases can be categorized as focal, multifocal, or infectious lesions. Diseases that manifest with focal lesions, such as cystic renal cell carcinoma, mixed epithelial and stromal tumor, and cystic nephroma, are often difficult to differentiate but have differing implications for follow-up after resection. Multifocal cystic renal lesions can be categorized as acquired or heritable. Acquired entities, such as glomerulocystic kidney disease, lithium-induced nephrotoxicity, acquired cystic kidney disease, multicystic dysplastic kidney, and localized cystic renal disease, often have distinct imaging and clinical features that allow definitive diagnosis. Heritable diseases, such as autosomal dominant polycystic kidney disease, von Hippel-Lindau disease, and tuberous sclerosis, are usually easily identified and have various implications for patient management. Infectious diseases have varied imaging appearances, and the possibility of infection must not be overlooked when assessing a cystic renal lesion. A thorough understanding of the spectrum of cystic renal disease will allow the radiologist to make a more specific diagnosis and provide the clinician with optimal recommendations for further diagnostic testing and follow-up imaging.

PO-0786 Prenatal Diagnosis Of Glomerulocystic Kidney Disease Due To Mutation Hnf 1b. Importance Of Genetic Test

Background HNF 1B is a key factor for the normal development of the kidney and pancreas transcription. Mutations affecting the gene encoding this factor are related to different phenotypes of renal disease among glomerulocystic kidney disease (GCKD) is included. GCKD is entity characterised by glomerular cysts with dilatation of the Bowman space and adjacent tubules. Methods Case report: Male patient, 7 years old, with renal cystic disease prenatal diagnosis of bilateral cortical cysts distribution. Unrelated parents, mother with IgA nephropathy, no alterations of hepatic metabolism or glucose. At birth, had very enlarged kidneys with increased echogenicity and loss of cortico medullary differentiation without other extrarenal findings. The disease has slowly evolved, with increased number of cysts, always cortical distribution. No impairment of renal function, normal BP. Genetic study was performed. Results Heterozygous mutation HNF 1B was identified (c. 1-?_1674+del), consisting of the deletion in one of its complete gene alleles. Neither parent is a carrier of the mutation. Conclusions The demonstration of de novo gene mutation in this patient confirms the aetiology of cystic disease. The test is very useful because it allows early diagnosis, non-invasive, allows estimating a prognosis and genetic counselling to the family.

Uromodulin: old friend with new roles in health and disease

The most abundant urinary protein, Tamm-Horsfall protein, later renamed uromodulin, is expressed exclusively by the thick ascending limb cells of the kidney and released into urine from the apical cell membrane. Uromodulin is believed to protect against urinary tract infections and stones, but its other physiologic functions have remained obscure until recently. Renewed interest in uromodulin has been brought about by the identification of uromodulin mutations as causes of a discrete group of diseases that are distinct from nephronophthisis. The three overlapping clinical uromodulin-associated kidney diseases (UAKD) are medullary cystic disease type 2, familial juvenile hyperuricemic nephropathy and glomerulocystic kidney disease. Previously thought of as "adult diseases", it is now recognized that they may also present in childhood and even in infancy. Common characteristics of all three diseases are autosomal dominant inheritance, unremarkable urine sediment and slow progression to end-stage renal disease (ESRD). They are frequently associated with hyperuricemia and gout. These diseases appear to result from failure of the mutant uromodulin to be incorporated into the apical cilium, thereby placing UAKD in the category of "ciliopathies". In addition to causing specific UAKD, certain uromodulin gene polymorphisms have been linked to ESRD in general, suggesting that uromodulin plays a modulatory role in kidney disease progression.

Scaffolding Proteins DLG1 and CASK Cooperate to Maintain the Nephron Progenitor Population during Kidney Development

DLG1 (discs-large homolog 1) and CASK (calcium/calmodulin-dependent serine protein kinase) interact at membrane-cytoskeleton interfaces and function as scaffolding proteins that link signaling molecules, receptors, and other scaffolding proteins at intercellular and synaptic junctions. Dlg1-null mice exhibit hydronephrosis, hydroureter, and occasionally hypoplastic kidneys, whereas Cask-null mice do not. To investigate whether DLG1 and CASK cooperate in the developing urogenital system, we generated mice deficient in both DLG1 and CASK either 1) globally, 2) in metanephric mesenchyme, or 3) in nephron progenitors. With each approach, Dlg1;Cask double-knockout (DKO) kidneys were severely hypoplastic and dysplastic and demonstrated rapid, premature depletion of nephron progenitors/stem cells. Several cellular and molecular defects were observed in the DKO kidneys, including reduced proliferation and increased apoptosis of cells in the nephrogenic zone and a progressive decrease in the number of cells expressing SIX2, a transcription factor essential for maintaining nephron progenitors. Fgf8 expression was reduced in early-stage DKO metanephric mesenchyme, accompanied by reduced levels of components of the Ras pathway, which is activated by fibroblast growth factor (FGF) signaling. Moreover, Dlg1(+/-);Cask(-/-) (het/null) kidneys were moderately hypoplastic and demonstrated impaired aggregation of SIX2-positive cells around the ureteric bud tips. Nephron progenitor-specific het/null mice survived with small kidneys but developed glomerulocystic kidney disease and renal failure. Taken together, these results suggest that DLG1 and CASK play critical cooperative roles in maintaining the nephron progenitor population, potentially via a mechanism involving effects on FGF signaling.

Unilateral glomerulocystic kidney disease associated with tuberous sclerosis complex in a neonate

We report a case of glomerular cystic kidney disease (GCKD) associated with tuberous sclerosis complex (TSC) in a neonate. The patient displayed progressive abdominal enlargement attributed to GCKD associated with TSC. After birth, the right kidney was resected because it compressed his liver and right lung, and possible malignancy could not be excluded. Macroscopically, the resected kidney was markedly enlarged, and histologically the kidney had numerous glomerular cysts accompanied by papillary epithelial growth. Notably, a small area of normal parenchyma was observed at the lower pole. The epithelial cells of the cysts displaying a papillary growth pattern were positive for mTOR, phosphorylated mTOR, and phosphorylated S6 ribosomal protein (p-S6). The morphologically noncystic, normal-looking tubular epithelium was also positive for p-S6. These results imply that one more molecular event might be necessary for cyst formation in GCKD associated with TSC, in addition to the activation of mTOR signaling.

Insuffisance rénale et maladies kystiques du rein

Cystic kidney diseases often are discovered at the time of initial work-up of renal failure through ultrasound or family history, or incidentally at the time of an imaging test. Hereditary diseases include autosomal dominant or recessive polycystic kidney disease (PKD), tuberous sclerosis (TS) and medullary cystic kidney disease (MCKD). Autosomal dominant PKD is characterized by large renal cysts developing in young adults. Renal failure is progressive and becomes severe around 50–60 years of age. Atypical cysts (hemorrhagic or hyperdense) are frequent on CT and MRI examinations. Imaging plays a valuable role in the management of acute complications such as cyst hemorrhage or infection. Autosomal recessive PKD is often detected in neonates, infants or young adults. It is characterized by renal enlargement due to the presence of small cysts and liver disease (fibrosis and biliary ductal dilatation). Late manifestation or slow progression of autosomal recessive PKD may be more difficult to distinguish from autosomal dominant PKD. These cystic kidney diseases should not be confused with non-hereditary incidental multiple renal cysts. In tuberous sclerosis, renal cysts are associated with angiomyolipomas and sometimes pulmonary lymphangioleiomyomatosis. Renal failure is inconstant. Other hereditary cystic kidney diseases, including MCKD and nephronophtisis, are usually associated with renal failure. Non-hereditary cystic kidney diseases include multicystic renal dysplasia (due to complete pelvi-ureteric atresia or hydronephrosis), acquired multicystic kidney disease (chronic renal failure, chronic hemodialysis) and varied cystic kidney diseases (multicystic renal disease, glomerulocystic kidney disease, microcystic kidney disease).

Tamm-Horsfall Glycoprotein Interacts with Renal Outer Medullary Potassium Channel ROMK2 and Regulates Its Function

Tamm-Horsfall glycoprotein (THGP) or Uromodulin is a membrane protein exclusively expressed along the thick ascending limb (TAL) and early distal convoluted tubule (DCT) of the nephron. Mutations in the THGP encoding gene result in Familial Juvenile Hyperuricemic Nephropathy (FJHN), Medullary Cystic Kidney Disease type 2 (MCKD-2), and Glomerulocystic Kidney Disease (GCKD). The physicochemical and biological properties of THGP have been studied extensively, but its physiological function in the TAL remains obscure. We performed yeast two-hybrid screening employing a human kidney cDNA library and identified THGP as a potential interaction partner of the renal outer medullary potassium channel (ROMK2), a key player in the process of salt reabsorption along the TAL. Functional analysis by electrophysiological techniques in Xenopus oocytes showed a strong increase in ROMK current amplitudes when co-expressed with THGP. The effect of THGP was specific for ROMK2 and did not influence current amplitudes upon co-expression with Kir2.x, inward rectifier potassium channels related to ROMK. Single channel conductance and open probability of ROMK2 were not altered by co-expression of THGP, which instead increased surface expression of ROMK2 as determined by patch clamp analysis and luminometric surface quantification, respectively. Despite preserved interaction with ROMK2, disease-causing THGP mutants failed to increase its current amplitude and surface expression. THGP(-/-) mice exhibited increased ROMK accumulation in intracellular vesicular compartments when compared with WT animals. Therefore, THGP modulation of ROMK function confers a new role of THGP on renal ion transport and may contribute to salt wasting observed in FJHN/MCKD-2/GCKD patients.

Glomerulocystic Kidney: One Hundred–Year Perspective

Glomerular cysts, defined as Bowman space dilatation greater than 2 to 3 times normal size, are found in disorders of diverse etiology and with a spectrum of clinical manifestations. The term glomerulocystic kidney (GCK) refers to a kidney with greater than 5% cystic glomeruli. Although usually a disease of the young, GCK also occurs in adults. To assess the recent molecular genetics of GCK, review our files, revisit the literature, and perform in silico experiments. We retrieved 20 cases from our files and identified more than 230 cases published in the literature under several designations. Although GCK is at least in part a variant of autosomal dominant or recessive polycystic kidney disease (PKD), linkage analysis has excluded PKD-associated gene mutations in many cases of GCK. A subtype of familial GCK, presenting with cystic kidneys, hyperuricemia, and isosthenuria is due to uromodullin mutations. In addition, the familial hypoplastic variant of GCK that is associated with diabetes is caused by mutations in TCF2, the gene encoding hepatocyte nuclear factor-1beta. The term GCK disease (GCKD) should be reserved for the latter molecularly recognized/inherited subtypes of GCK (not to include PKD). Review of our cases, the literature, and our in silico analysis of the overlapping genetic entities integrates established molecular-genetic functions into a proposed model of glomerulocystogenesis; a classification scheme emerged that (1) emphasizes the clinical significance of glomerular cysts, (2) provides a pertinent differential diagnosis, and (3) suggests screening for probable mutations.

Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression

Uromodulin (UMOD) mutations are responsible for three autosomal dominant tubulo-interstitial nephropathies including medullary cystic kidney disease type 2 (MCKD2), familial juvenile hyperuricemic nephropathy and glomerulocystic kidney disease. Symptoms include renal salt wasting, hyperuricemia, gout, hypertension and end-stage renal disease. MCKD is part of the 'nephronophthisis-MCKD complex', a group of cystic kidney diseases. Both disorders have an indistinguishable histology and renal cysts are observed in either. For most genes mutated in cystic kidney disease, their proteins are expressed in the primary cilia/basal body complex. We identified seven novel UMOD mutations and were interested if UMOD protein was expressed in the primary renal cilia of human renal biopsies and if mutant UMOD would show a different expression pattern compared with that seen in control individuals. We demonstrate that UMOD is expressed in the primary cilia of renal tubules, using immunofluorescent studies in human kidney biopsy samples. The number of UMOD-positive primary cilia in UMOD patients is significantly decreased when compared with control samples. Additional immunofluorescence studies confirm ciliary expression of UMOD in cell culture. Ciliary expression of UMOD is also confirmed by electron microscopy. UMOD localization at the mitotic spindle poles and colocalization with other ciliary proteins such as nephrocystin-1 and kinesin family member 3A is demonstrated. Our data add UMOD to the group of proteins expressed in primary cilia, where mutations of the gene lead to cystic kidney disease.