Carbonic Anhydrase 2 Deletion Delays the Growth of Kidney Cysts Whereas Foxi1 Deletion Completely Abrogates Cystogenesis in TSC.

Tuberous sclerosis complex (TSC) presents with renal cysts and benign tumors, which eventually lead to kidney failure. The factors promoting kidney cyst formation in TSC are poorly understood. Inactivation of carbonic anhydrase 2 (Car2) significantly reduced, whereas, deletion of Foxi1 completely abrogated the cyst burden in Tsc1 KO mice. In these studies, we contrasted the ontogeny of cyst burden in Tsc1/Car2 dKO mice vs. Tsc1/Foxi1 dKO mice. Compared to Tsc1 KO, the Tsc1/Car2 dKO mice showed few small cysts at 47 days of age. However, by 110 days, the kidneys showed frequent and large cysts with overwhelming numbers of A-intercalated cells in their linings. The magnitude of cyst burden in Tsc1/Car2 dKO mice correlated with the expression levels of Foxi1 and was proportional to mTORC1 activation. This is in stark contrast to Tsc1/Foxi1 dKO mice, which showed a remarkable absence of kidney cysts at both 47 and 110 days of age. RNA-seq data pointed to profound upregulation of Foxi1 and kidney-collecting duct-specific H+-ATPase subunits in 110-day-old Tsc1/Car2 dKO mice. We conclude that Car2 inactivation temporarily decreases the kidney cyst burden in Tsc1 KO mice but the cysts increase with advancing age, along with enhanced Foxi1 expression.

Contrast-Enhanced Ultrasound as a Diagnostic Procedure in Renal Diseases: A Case Report.

Standard ultrasound (US) finds wide use in renal diseases as a screening procedure, but it is not always able to characterize lesions, especially in differential diagnosis between benign and malignant lesions. In contrast, contrast-enhanced ultrasonography (CEUS) is appropriate in differentiating between solid and cystic lesions as well as between tumors and pseudotumors. We show the case of a nephropathic patient who showed a complex, large, growing renal mass, characterized through a CEUS. This seventy-five-year-old diabetic heart patient showed a 6 cm-complex and plurisected cyst on ultrasound of left kidney. Laboratory data showed the presence of stage IIIb chronic renal failure with GFR 30 ml/min, creatinine 2.33 mg/dl, azotemia 88 mg/dl. The patient performed abdominal CT without contrast medium, showing at the level of the left upper pole, a roundish formation with the dimensions of approximately 70x53x50 mm. At the semiannual checkup, the nephrology examination showed a slight rise in creatinine and, therefore, after six months, it was decided to perform a CT scan without contrast medium again. CT showed a slight increase in the size of the mass located at the left kidney (74x56x57 mm). Given the increased size of the left mass, albeit modest, a CEUS was performed to reach a diriment diagnosis. CEUS concluded for complex cystic formation with presence of intraluminal solid-corpuscular material, with thrombotic-hemorrhagic etiology, in progressive phase of organization, classifiable as Bosniak type II cyst. CEUS in the kidneys is a cost-effective and valuable imaging technique; it is accurate in the characterization of indeterminate lesions and complex cysts.

Joubert syndrome presenting bilateral peroneal neuropathies: A case report.

RATIONALE: Joubert syndrome (JS) is a rare genetic disorder that presents with various neurological symptoms, primarily involving central nervous system dysfunction. Considering the etiology of JS, peripheral nervous system abnormalities cannot be excluded; however, cases of JS accompanied by peripheral nervous system abnormalities have not yet been reported. Distinct radiological findings on brain magnetic resonance imaging were considered essential for the diagnosis of JS. However, recently, cases of JS with normal or nearly normal brain morphology have been reported. To date, there is no consensus on the most appropriate diagnostic method for JS when imaging-based diagnostic approach is challenging. This report describes the case of an adult patient who exhibited bilateral peroneal neuropathies and was finally diagnosed with JS through genetic testing. PATIENT CONCERNS AND DIAGNOSIS: A 27-year-old man visited our outpatient clinic due to a gait disturbance that started at a very young age. The patient exhibited difficulty maintaining balance, especially when walking slowly. Oculomotor apraxia was observed on ophthalmic evaluation. During diagnostic workups, including brain imaging and direct DNA sequencing, no conclusive findings were detected. Only nerve conduction studies revealed profound bilateral peroneal neuropathies. We performed whole genome sequencing to obtain a proper diagnosis and identify the gene mutation responsible for JS. LESSONS: This case represents the first instance of peripheral nerve dysfunction in JS. Further research is needed to explore the association between JS and peripheral nervous system abnormalities. Detailed genetic testing may serve as a valuable tool for diagnosing JS when no prominent abnormalities are detected in brain imaging studies.

Syndromic ciliopathy: a taiwanese single-center study.

BACKGROUND: Syndromic ciliopathies are a group of congenital disorders characterized by broad clinical and genetic overlap, including obesity, visual problems, skeletal anomalies, mental retardation, and renal diseases. The hallmark of the pathophysiology among these disorders is defective ciliary functions or formation. Many different genes have been implicated in the pathogenesis of these diseases, but some patients still remain unclear about their genotypes. METHODS: The aim of this study was to identify the genetic causes in patients with syndromic ciliopathy. Patients suspected of or meeting clinical diagnostic criteria for any type of syndromic ciliopathy were recruited at a single diagnostic medical center in Southern Taiwan. Whole exome sequencing (WES) was employed to identify their genotypes and elucidate the mutation spectrum in Taiwanese patients with syndromic ciliopathy. Clinical information was collected at the time of patient enrollment. RESULTS: A total of 14 cases were molecularly diagnosed with syndromic ciliopathy. Among these cases, 10 had Bardet-Biedl syndrome (BBS), comprising eight BBS2 patients and two BBS7 patients. Additionally, two cases were diagnosed with Alström syndrome, one with Oral-facial-digital syndrome type 14, and another with Joubert syndrome type 10. A total of 4 novel variants were identified. A recurrent splice site mutation, BBS2: c.534 + 1G > T, was present in all eight BBS2 patients, suggesting a founder effect. One BBS2 patient with homozygous c.534 + 1G > T mutations carried a third ciliopathic allele, TTC21B: c.264_267dupTAGA, a nonsense mutation resulting in a premature stop codon and protein truncation. CONCLUSIONS: Whole exome sequencing (WES) assists in identifying molecular pathogenic variants in ciliopathic patients, as well as the genetic hotspot mutations in specific populations. It should be considered as the first-line genetic testing for heterogeneous disorders characterized by the involvement of multiple genes and diverse clinical manifestations.

The Phenotypic Variability Associated with Hepatocyte Nuclear Factor 1B Genetic Defects Poses Challenges in Both Diagnosis and Therapy.

The evolving landscape of clinical genetics is becoming increasingly relevant in the field of nephrology. HNF1B-associated renal disease presents with a diverse array of renal and extrarenal manifestations, prominently featuring cystic kidney disease and diabetes mellitus. For the genetic analyses, whole exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA) were performed. Bioinformatics analysis was performed with Ingenuity Clinical Insights software (Qiagen). The patient's electronic record was utilized after receiving informed consent. In this report, we present seven cases of HNF1B-associated kidney disease, each featuring distinct genetic abnormalities and displaying diverse extrarenal manifestations. Over 12 years, the mean decline in eGFR averaged -2.22 ± 0.7 mL/min/1.73 m2. Diabetes mellitus was present in five patients, kidney dysplastic lesions in six patients, pancreatic dysplasia, hypomagnesemia and abnormal liver function tests in three patients each. This case series emphasizes the phenotypic variability and the fast decline in kidney function associated with HNF-1B-related disease. Additionally, it underscores that complex clinical presentations may have a retrospectively straightforward explanation through the use of diverse genetic analytical tools.

Development of crizotinib-associated renal cyst in a non-small cell lung cancer patient with ALK fusion: a case report and review of the literature.

BACKGROUND: Crizotinib, an oral first-generation tyrosine kinase inhibitor (TKI), is superior to systemic chemotherapy for the treatment of non-small cell lung cancer (NSCLC) with positive rearrangement of anaplastic lymphoma kinase (ALK). However, an increased incidence of renal and hepatic cysts has been reported in the patients on crizotinib treatment. CASE PRESENTATION: Here, we describe a case of a 71-year-old Chinese women developed multiple cystic lesions in kidney and liver during crizotinib treatment for the primary and metastatic NSCLC. The renal and hepatic cysts were noted by CT scan 3 months after crizotinib treatment, which were spontaneously and significantly regressed after stopping crizotinib. CONCLUSIONS: Based on literature review and our experience in this case report, we concluded that crizotinib-associated renal cyst (CARCs) has features of malignancy and abscess in radiographic imaging, and thus, pathological confirmation is necessary to avoid inappropriate treatment decision. In addition, to benefit the patients with progress-free survival (PFS), switching from crizotinib to alectinib is recommended for the treatment of NSCLC patients who developed CARCs.

[A case of crizotinib-associated renal cysts].

Crizotinib-associated renal cysts (CARC) are the development of new renal cysts or pre-existing renal cysts after the treatment with crizotinib. Most CARC disappear after crizotinib is stopped. A few CARC showed aggressive behavior that could go beyond the invasion of the renal cortex into nearby structures, including perirenal space, psoas major muscle, intestine, and abdominal wall. A case of EML4-ALK fusion mutation in invasive lung adenocarcinoma has been reported. Multiple cystic changes occurred repeatedly in both kidneys, right rectus muscle, and psoas major muscle after treatment with crizotinib, and spontaneous absorption and resolution after discontinuation of the drug.

Japanese 17q12 Deletion Syndrome with Complex Clinical Manifestations.

17q12 deletion syndrome is a rare chromosomal anomaly with variable phenotypes, caused by the heterozygous deletion of chromosome 17q12. We herein report a 35-year-old Japanese patient with chromosomal 17q12 deletion syndrome identified by de novo deletion of the 1.46 Mb segment at the 17q12 band by genetic analyses. He exhibited a wide range of phenotypes, such as maturity-onset diabetes of the young (MODY) type 5, structural or functional abnormalities of the kidney, liver, and pancreas; facial dysmorphic features, electrolyte disorders; keratoconus, and acquired perforating dermatosis. This case report provides valuable resources concerning the clinical spectrum of rare 17q12 deletion syndrome.

Joubert syndrome-derived induced pluripotent stem cells show altered neuronal differentiation in vitro.

Joubert syndrome (JS) is a recessively inherited congenital ataxia characterized by hypotonia, psychomotor delay, abnormal ocular movements, intellectual disability, and a peculiar cerebellar and brainstem malformation, the "molar tooth sign." Over 40 causative genes have been reported, all encoding for proteins implicated in the structure or functioning of the primary cilium, a subcellular organelle widely present in embryonic and adult tissues. In this paper, we developed an in vitro neuronal differentiation model using patient-derived induced pluripotent stem cells (iPSCs), to evaluate possible neurodevelopmental defects in JS. To this end, iPSCs from four JS patients harboring mutations in distinct JS genes (AHI1, CPLANE1, TMEM67, and CC2D2A) were differentiated alongside healthy control cells to obtain mid-hindbrain precursors and cerebellar granule cells. Differentiation was monitored over 31 days through the detection of lineage-specific marker expression by qRT-PCR, immunofluorescence, and transcriptomics analysis. All JS patient-derived iPSCs, regardless of the mutant gene, showed a similar impairment to differentiate into mid-hindbrain and cerebellar granule cells when compared to healthy controls. In addition, analysis of primary cilium count and morphology showed notable ciliary defects in all differentiating JS patient-derived iPSCs compared to controls. These results confirm that patient-derived iPSCs are an accessible and relevant in vitro model to analyze cellular phenotypes connected to the presence of JS gene mutations in a neuronal context.

First case of nodular dermatofibrosis with cystic renal disease in a beagle: An atypical case without FLCN gene mutation.

This report presents the first case of nodular dermatofibrosis with renal cysts (NDRC) in a beagle. In this atypical case, the gene mutation associated with the disease was not present, the renal cysts showed dynamic changes in size and number, and the patient has greatly surpassed the NDRC life expectation.

Value of virtual non-contrast images to identify uncomplicated cystic renal lesions: photon-counting detector CT vs. dual-energy integrating detector CT.

PURPOSE: To investigate the value of photon-counting detector CT (PCD-CT) derived virtual non-contrast (VNC) reconstructions to identify renal cysts in comparison with conventional dual-energy integrating detector (DE EID) CT-derived VNC reconstructions. MATERIAL AND METHODS: We prospectively enrolled consecutive patients with simple renal cysts (Bosniak classification-Version 2019, density ≤ 20 HU and/or enhancement ≤ 20 HU) who underwent multiphase (non-contrast, arterial, portal venous phase) PCD-CT and for whom non-contrast and portal venous phase DE EID-CT was available. Subsequently, VNC reconstructions were calculated for all contrast phases and density as well as contrast enhancement within the cysts were measured and compared. MRI and/or ultrasound served as reference standards for lesion classification. RESULTS: 19 patients (1 cyst per patient; age 69.5 ± 10.7 years; 17 [89.5%] male) were included. Density measurements on PCD-CT non-contrast and VNC reconstructions (arterial and portal venous phase) revealed no significant effect on HU values (p = 0.301). In contrast, a significant difference between non-contrast vs. VNC images was found for DE EID-CT (p = 0.02). For PCD-CT, enhancement for VNC reconstructions was < 20 HU for all evaluated cysts. DE EID-CT measurements revealed an enhancement of > 20 HU in five lesions (26.3%) using the VNC reconstructions, which was not seen with the non-contrast images. CONCLUSION: PCD-CT-derived VNC images allow for reliable and accurate characterization of simple cystic renal lesions similar to non-contrast scans whereas VNC images calculated from DE EID-CT resulted in substantial false characterization. Thus, PCD-CT-derived VNC images may substitute for non-contrast images and reduce radiation dose and follow-up imaging.

Diagnosis and Surgical Treatment of a Renal Cyst Causing Unilateral Lameness in a Golden Eagle (Aquila chrysaetos).

This report describes the diagnosis and treatment of a benign renal cyst in an adult, female golden eagle (Aquila chrysaetos) presented for unilateral leg lameness. A cyst at the cranial division of the left kidney was diagnosed by computed tomography and was suspected of compressing the lumbosacral nerve plexus, resulting in limb lameness. The renal cyst was incompletely excised because the cyst wall was closely adhered to the kidney parenchyma and local blood supply. Fluid analysis and surgical biopsy of the cyst and left kidney confirmed the diagnosis of a benign renal cyst. No evidence of an infectious, inflammatory, or neoplastic etiology was noted. Postoperatively, the eagle's lameness resolved and the bird was ultimately released following recovery. During treatment for the renal cyst, the eagle was concurrently found to have increased serum titers on elementary body agglutination for Chlamydia psittaci and a positive titer for Aspergillus species antibody testing. The bird was administered doxycycline, azithromycin, and voriconazole for treatment of these potential pathogens prior to release. Unfortunately, the eagle was found dead 86 days postrelease due to an unknown cause. To the authors' knowledge, this is the first report of a golden eagle with a benign solitary renal cyst causing unilateral lameness secondary to nerve compression that was resolved with surgical excision.

High Incidence of CPLANE1-Related Joubert Syndrome in the Products of Conceptions from Early Pregnancy Losses

Background: The fetal monogenic causes of early pregnancy losses (EPLs) are mainly unknown, with only a few articles on the subject published. In our previous study of EPLs using whole-exome sequencing analysis, we confirmed a genetic diagnosis of CPLANE1-related Joubert syndrome (JS) in three EPLs from two couples and identified a relatively common CPLANE1 allele among our population (NM_001384732.1:c.1819delT;c.7817T>A, further after referred as "complex allele"). Pathogenic variants in the CPLANE1 (C5orf42) gene are reported to cause JS type 17, a primary ciliopathy with various system defects. Aims: To examine the hypothesis that the CPLANE1 "complex allele," whether homozygous or compound heterozygous, is a common cause of EPLs in our population. Study Design: Cohort study/case-control study.ontrol study. Methods: In this study, we used polymerase chain reaction-based methods to screen for CPLANE1 "complex allele" presence among 246 euploid EPLs (< 12 gestational weeks) from families in North Macedonia. We also investigated the impact of this allele in 650 women with EPLs versus 646 women with no history of pregnancy loss and at least one livebirth, matched by ethnic origin. Results: We found a high incidence of JS in the total study group of EPLs (2.03%), with a considerably higher incidence among Albanian families (6.25%). Although not statistically significant, women with EPLs had a higher allele frequency of the CPLANE1 "complex allele" (AF = 1.38%) than the controls (AF = 0.85%; p = 0.2). Albanian women had significantly higher frequency of the "complex allele" than the Macedonians (AF = 1.65% and 0.39%, respectively; p = 0.003). Conclusion: To the best of our knowledge, this is the highest reported incidence of fetal monogenic disease that might cause EPLs. Targeted screening for the CPLANE1 "complex allele" would be warranted in Albanian ethnic couples because it would detect one JS in every 16 euploid EPLs. Our findings have a larger impact on the pathogenesis of pregnancy loss and contribute to a better understanding of the pathogenicity of the variants in the CPLANE1 gene.

Multiple and large simple renal cysts are associated with glomerular filtration rate decline: a cross-sectional study of Chinese population.

BACKGROUND: Although simple renal cyst (SRC) is a kind of structural alterations of kidney with age, the relationship between SRC and renal function is still obscure. We investigated the relationship between SRC and renal function in Chinese population. METHODS: The medical records of 41,842 individuals who underwent physical examinations at the Health Check-up Center at our institution in 2018 were reviewed. According to whether with SRC, they were divided into no-SRC and SRC groups. SRCs were classified into subgroups based on number (< 2 vs. ≥ 2) and size (< 2 cm vs. ≥ 2 cm). Logistic regression was used to examine the relationship between SRC and estimated glomerular filtration rate (eGFR). RESULTS: Multinomial logistic regression analysis showed that the adjusted odds ratio (OR) for eGFR slight decline in subjects with SRC was 1.26(95% confidence interval (95% CI):1.17-1.35, p < 0.001), and the OR for eGFR severe decline was 1.35(95% CI: 1.16-1.56, p < 0.001) compared with no-SRC. The adjusted OR of SRC number ≥ 2 and ≥ 2 cm on the risk of eGFR severe decline was the highest (OR:1.68, 95% CI:1.25-2.23, p < 0.01) of four SRC subgroups. CONCLUSIONS: SRC is related to eGFR decline, especially when the person with one more SRCs and the size of SRC is more than 2 cm. SRC could be a warning sign for clinicians to judge the decline of renal function.

Joubert syndrome causing mutation in C2 domain of CC2D2A affects structural integrity of cilia and cellular signaling molecules.

Cilia are organelles extend from cells to sense external signals for tuning intracellular signaling for optimal cellular functioning. They have evolved sensory and motor roles in various cells for tissue organization and homeostasis in development and post-development. More than a thousand genes are required for cilia function. Mutations in them cause multisystem disorders termed ciliopathies. The null mutations in CC2D2A result in Meckel syndrome (MKS), which is embryonic lethal, whereas patients who have missense mutations in the C2 domain of CC2D2A display Joubert syndrome (JBTS). They survive with blindness and mental retardation. How C2 domain defects cause disease conditions is not understood. To answer this question, C2 domain of Cc2d2a (mice gene) was knocked down (KD) in IMCD-3 cells by shRNA. This resulted in defective cilia morphology observed by immunofluorescence analysis. To further probe the cellular signaling alteration in affected cells, gene expression profiling was done by RNAseq and compared with the controls. Bioinformatics analysis revealed that the differentially expressed genes (DEGs) have functions in cilia. Among the 61 cilia DEGs identified, 50 genes were downregulated and 11 genes were upregulated. These cilia genes are involved in cilium assembly, protein trafficking to the cilium, intraflagellar transport (IFT), cellular signaling like polarity patterning, and Hedgehog signaling pathway. This suggests that the C2 domain of CC2D2A plays a critical role in cilia assembly and molecular signaling hosted in cilia for cellular homeostasis. Taken together, the missense mutations in the C2 domain of CC2D2A seen in JBTS might have affected cilia-mediated signaling in neurons of the retina and brain.

Novel compound heterozygous variants in ARL13B lead to Joubert syndrome.

Joubert syndrome (JBTS) is a systematic developmental disorder mainly characterized by a pathognomonic mid-hindbrain malformation. All known JBTS-associated genes encode proteins involved in the function of antenna-like cellular organelle, primary cilium, which plays essential roles in cellular signal transduction and development. Here, we identified four unreported variants in ARL13B in two patients with the classical features of JBTS. ARL13B is a member of the Ras GTPase family and functions in ciliogenesis and cilia-related signaling. The two missense variants in ARL13B harbored the substitutions of amino acids at evolutionarily conserved positions. Using model cell lines, we found that the accumulations of the missense variants in cilia were impaired and the variants showed attenuated functions in ciliogenesis or the trafficking of INPP5E. Overall, these findings expanded the ARL13B pathogenetic variant spectrum of JBTS.

The Predictive Power of Bosniak 3 and 4 Cystic Renal Lesion Categorization Using Contrast-Enhanced Ultrasound.

OBJECTIVES: Contrast-enhanced ultrasound (CEUS) is increasingly utilized for the noninvasive assessment of renal cystic lesions, using the Bosniak grading system. Bosniak 3-4 lesions require surgical referral, which allows correlation with the histopathological outcome. METHODS: In this single-center, retrospective study we evaluated renal CEUS exams conducted with SonoVue® with a diagnosis of a Bosniak 3 or 4 lesion between 2019 and 2022. A total of 49 patients and 50 lesions met the inclusion criteria, 31 lesions had available histopathological results. Patient demographics, cyst morphology, and dominant imaging features were registered. The histopathological diagnosis was considered a reference standard. RESULTS: Positive predictive power (PPV) for neoplastic lesions was comparable in the Bosniak 3 and 4 categories (75 vs 93.3%, P = .33), while PPV for histopathologically malignant lesion was considerably higher in the latter group (25 vs 93.33%, P = .0002). None of the lesions which had vividly enhancing thin septa as their dominant CEUS feature were malignant. Oncocytoma, multilocular cystic renal neoplasm of low malignant potential, and cystic nephroma were the major benign entities among Bosniak 3 lesions. Localized cystic kidney disease and hemorrhagic cysts were found to be the primary mimickers leading to false positive imaging findings. CONCLUSIONS: CEUS has a high predictive power for malignancy in the Bosniak 4 category, which is not maintained in the Bosniak 3 group due to the large proportion of benign lesions. Adherence to rigorous rule-in criteria and active surveillance strategies need to be considered for equivocal CEUS Bosniak 3 lesions.

Intra- and Interobserver Study Investigating the Adapted EFSUMB Bosniak Cyst Categorization Proposed for Contrast-Enhanced Ultrasound (CEUS) in 2020.

BACKGROUND: To investigate the inter- and intraobserver variability in comparison to an expert gold standard of the new and modified renal cyst Bosniak classification proposed for contrast-enhanced ultrasound findings (CEUS) by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) in 2020. MATERIALS AND METHODS: 84 CEUS examinations for the evaluation of renal cysts were evaluated retrospectively by six readers with different levels of ultrasound expertise using the modified Bosniak classification proposed for CEUS. All cases were anonymized, and each case was rated twice in randomized order. The consensus reading of two experts served as the gold standard, to which all other readers were compared. Statistical analysis was performed using Cohen's weighted kappa tests, where appropriate. RESULTS: Intraobserver variability showed substantial to almost perfect agreement (lowest kappa κ=0.74; highest kappa κ=0.94), with expert level observers achieving the best results. Comparison to the gold standard was almost perfect for experts (highest kappa κ=0.95) and lower for beginner and intermediate level readers still achieving mostly substantial agreement (lowest kappa κ=0.59). Confidence of rating was highest for Bosniak classes I and IV and lowest for classes IIF and III. CONCLUSION: Categorization of cystic renal lesions based on the Bosniak classification proposed by the EFSUMB in 2020 showed very good reproducibility. While even less experienced observers achieved mostly substantial agreement, training remains a major factor for better diagnostic performance.

Visual function in children with Joubert syndrome.

AIM: To describe visual function in children with Joubert syndrome and to investigate its possible association with diagnostic and developmental aspects. METHOD: This retrospective cross-sectional work included 59 patients (33 male; mean age 9 years 2 months, standard deviation 6 years 3 months, range 4 months to 23 years) diagnosed with Joubert syndrome from January 2002 to December 2020. Data about clinical (neurological, neuro-ophthalmological, developmental/cognitive) and diagnostic (e.g. genetic testing, neuroimaging, systemic involvement) evaluations were collected in a data set during a review of medical records. Clinical and diagnostic variables were described in terms of raw counts and percentages. A χ2 test was conducted to investigate their association with neuropsychological skills. RESULTS: Ocular motor apraxia was highly represented in our cohort (75%), with a high prevalence of refractive defects and retinal abnormalities. Developmental delay/intellectual disability was frequent (in 69.5% of the sample), associated with retinal dystrophy (p = 0.047) and reduced visual acuity both for near (p = 0.014) and for far distances (p = 0.017). INTERPRETATION: On the basis of the relevance of oculomotor and perceptual alterations and their impact on overall and cognitive impairment, we encourage early and multidisciplinary assessment and follow-up of visual function in children with Joubert syndrome. This would help in planning a personalized rehabilitation to sustain functional vision. Further studies will be important to explore the link between biological aspects and global functioning in children with Joubert syndrome. WHAT THIS PAPER ADDS: Perceptual deficits and oculomotor impairments frequently coexist in Joubert syndrome. Retinal dysfunction may be present despite the absence of funduscopic abnormalities. Both perceptual and oculomotor impairments negatively affect cognitive development in Joubert syndrome.

Decline in measured glomerular filtration rate is associated with simple renal cyst in Chinese patients with type 2 diabetes.

AIMS/INTRODUCTION: Simple renal cysts (SRC) are associated with age, hypertension and hyperuricemia, which are risk factors of renal impairment. This study aimed to investigate the prevalence of SRC and its association with measured glomerular filtration rate (mGFR) in patients with type 2 diabetes mellitus in China. METHODS: A total of 3,552 patients with type 2 diabetes mellitus admitted to Shanghai Sixth People's Hospital from January 2012 to December 2016 were investigated. All participants were diagnosed as SRC by color Doppler, and all participants were measured for GFR by using dynamic renal scintigraphy with technetium-99m-diethylene triamine peta-acetic acid. RESULTS: The prevalence of SRC was 17.4% (619 cases). Participants with SRC had significantly lower mGFR values than those without SRC (86.16 ± 26.20 vs 94.88 ± 23.98 mL/min/1.73 m2 , P < 0.001). In 478 participants with unilateral renal cyst, the mGFR of the kidney affected by SRC was significantly lower than that of the unaffected kidney (43.32 ± 13.74 vs 44.18 ± 13.34 mL/min/1.73 m2 , P = 0.014). The participants were divided into four groups according to the quartiles of mGFR level (≥109.50, 93.80-109.49, 76.90-93.79 and <76.90 mL/min/1.73 m2 ). The prevalence of SRC gradually increased with decreasing mGFR level (12.9, 13.9, 16.6 and 27.8%, respectively; P trend <0.01). After adjusting for age, sex, duration of diabetes, hypertension and other potential confounders, the logistic regression showed that SRC was an independent risk factor for impaired GFR (<60 mL/min/1.73 m2 ; odds ratio 1.656; 95% confidence interval 1.451-1.890, P < 0.001). CONCLUSION: SRC is an independent risk factor for the decrease of mGFR in Chinese diabetes patients, and could affect the renal GFR measured by dynamic renal scintigraphy on the SRC side.