Comprehensive molecular diagnosis of 67 Chinese Usher syndrome probands: high rate of ethnicity specific mutations in Chinese USH patients

Both Novel missense alleles identified in MYO7A genes are conserved between human, zebrafish and Drosophila melanogaster. (PPTX 676 kb

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Whole exome sequencing identified a novel truncation mutation in the NHS gene associated with Nance-Horan syndrome

Abstract Background Nance-Horan syndrome (NHS) is an X-linked inheritance disorder characterized by bilateral congenital cataracts, and facial and dental dysmorphism. This disorder is caused by mutations in the NHS gene. However, NHS may be difficult to detect in individuals with subtle facial dysmorphism and dental abnormalities in whom congenital cataracts are the primary clinical manifestations. Methods In this study, we present a three-generation family with NHS. Whole exome sequencing was performed to determine the potential pathogenic variant in the proband. Further validation was explored with Sanger sequencing in 9 of the available individuals of the family and additional 200 controls. Results A novel truncation mutation in gene NHS (c.C4449G, p.Tyr1483Ter) was found in the proband, who presented with a long-narrow face, prominent nose and large anteverted pinnae ear, screw-driver like incisors, mild mulberry like molars, one missing maxillary second molar and malocclusion. We found this mutation was detected in 2 male patients and 4 female carriers in the family. However, the mutation was never detected in the control subjects. Conclusions In conclusion, we identified a novel truncation mutation in the NHS gene, which might associate with NHS. Our review on the NHS studies illustrated that NHS has significantly clinical heterogeneity. And NHS mutations in the NHS-affected individuals typically result in premature truncation of the protein. And the new mutation revealed in this study would highlight the understanding of the causative mutations of NHS

Unilateral retinocytoma associated with a variant in the RB1 gene

Abstract Background Retinocytoma is a rare benign retinal tumor associated with variants in the RB1 gene. Ophthalmoscopic features can include a translucent retinal mass, calcification, retinal pigment epithelial alteration and chorioretinal atrophy. Methods Detailed ophthalmological examinations were performed in a Chinese patient with retinocytoma and his daughter with bilateral retinoblastoma. Sanger sequencing was performed to detect RB1 genetic variants in the patient, his daughter and tumor tissue from his daughter. Results A 33‐year‐old man presented with poor vision and strabismus in the right eye since childhood. Fundus examination revealed a round yellow‐white lesion stretching from the nasal side of the optic disc to the temporal periphery of the right eye. Sequencing result identified a reported variant (c.658C>G, p.Leu220Val) in the RB1 gene (NM_000321.2) of DNA extracted from peripheral blood of the patient and his daughter. The missense variant was also found in the tumor tissue from his daughter. Conclusions We report detailed clinical features and genetic analysis of a case with unilateral retinocytoma. Retinocytoma has a wide range of clinical phenotypes; genetic testing is therefore a useful tool for the diagnosis of atypical cases

Genetic and clinical characterization of mainland Chinese patients with sialidosis type 1

Abstract Background Sialidosis type 1 is a rare inherited disorder with a high disability. No genetically confirmed mainland Chinese patient with sialidosis type 1 has been reported. This study evaluated the phenotypes and genotypes of mainland Chinese patients with sialidosis type 1. Methods It was a retrospective case series study. Four unrelated patients were enrolled. Comprehensive clinical evaluations and molecular genetic analysis of the NEU1 gene were performed. Results Three out of four patients presented progressive myoclonus epilepsy. The best‐corrected visual acuity ranged from 20/2000 to 20/25. Punctate cataracts were found in all of the patients. Distinct macular cherry red spots were observed in three patients by fundoscopy, and a relatively normal fundus was revealed in one patient. Optical coherence tomography (OCT) showed increased reflectivity of the nerve fiber and ganglion cell layers, and fundus autofluorescence (FAF) revealed hyperautofluorescent areas surrounding the fovea in all of the patients. Only superficial retinal vessels can be observed using OCT angiography; the deeper capillary plexus could not be observed. Visual evoked potential revealed varying degrees of decreased amplitude and/or prolonged latency of P100 or P2 waves. The most frequent sequence variant identified was c.544A>G (p.S182G) (NM_000434.3). Conclusions Our study first described the ophthalmic and neurologic characteristics of a small cohort of unrelated mainland Chinese patients with sialidosis type 1. We found that c.544A>G (p. S182G) might be a hotspot variant in Chinese patients. The accumulation of metabolic products in the nerve fiber and ganglion cell layers is a characteristic ocular finding that could be sensitively detected by OCT and FAF imaging

Multidisciplinary Treatment on a Case of ROSAH Syndrome

A 15-year-old female was referred to the hospital with intermittent fever, where multiple systemic abnormalities were found, such as splenomegaly, secondary hypersplenism, retinitis pigmentosa, and ectodermal dysplasia. Medical history revealed that she had suffered recurrent respiratory infections, blurred vision at night, and dysplasia of teeth and nail beds since childhood. Then she was suspected to be experiencing ROSAH syndrome, a rare disease newly recognized in recent years, which was finally confirmed by gene sequencing results. During a course of treatment with tumor necrosis factor inhibitors, recurrent fever with elevated inflammatory markers reappeared, and the child developed headaches. To guide the comprehensive treatment and improve the patient's quality of life, the multidisciplinary team in Peking Union Medical College Hospital discussed together and directed the following treatment