Humans ; Kidney Diseases ; genetics ; Mutation ; WT1 Proteins ; genetics

OBJECTIVE: To explore the clinical features and genomic abnorm ality of a fetus enlarged multicystic dysplastic kidneys with oligohydramnios caused by NPHP3 gene mutation. METHODS: The fetuse was found to have multicystic dysplastic kidneys with oligohydramnios upon ultrasonography during the second trimester. Following induced abortion, fetal tissue was collected for the extraction of DNA, chromosomal microarray analysis (CMA) and whole exome sequencing (WES). Sanger sequencing was used to verify the suspected variants in the family. RESULTS: Antenatal ultrasound examination at 19 weeks showed "polycystic" kidneys with Oligohydramnios. Delivery was by induced labour because of the critically low amniotic fluid volume. Testing of CMA was normal. WES showed a compound heterozygous mutation of c.1817G>A, p.W606X; c.432dupA, p.E145Rfs*18 mutations are novel mutations in this study. CONCLUSION The research may further expand the NPHP3 gene mutation spectrum. Enlarged multicystic dysplastic kidneys with oligohydramnios caused by NPHP3 gene mutation at least include one or two splice site mutation, frameshift mutation or nonsense mutation foetal poor prognosis.
Amniotic Fluid ; Female ; Humans ; Kidney Diseases, Cystic ; Multicystic Dysplastic Kidney/genetics* ; Mutation ; Oligohydramnios/genetics* ; Polycystic Kidney Diseases ; Pregnancy ; Ultrasonography, Prenatal

Nephronophthisis (NPHP) is a group of autosomal recessive tubulointerstitial cystic kidney disorders. This article reports a case of NPHP type 12 caused by TTC21B mutations. The girl had an insidious onset, with moderate proteinuria, renal dysfunction, stage 2 hypertension, situs inversus, and short phalanges when she visited the hospital for the first time at the age of 3 years and 6 months. The renal lesions progressed to end-stage renal disease (ESRD) before she was 4 years old. Urine protein electrophoresis showed glomerular proteinuria. There were significant increases in urinary β2-microglobulin and α1-microglobulin. Gene detection revealed two compound heterozygous mutations, c.1552T>C (p.C518R) and c.752T>G (p.M251R), in the TTC21B gene, which came from her father and mother respectively. The c.752T>G mutation was a novel mutation. It is concluded that besides typical tubular changes of NPHP, marked glomerular damage is also observed in patients with TTC21B gene mutations.
Child, Preschool ; Female ; Genotype ; Humans ; Kidney ; Kidney Diseases, Cystic ; Kidney Failure, Chronic ; Microtubule-Associated Proteins ; genetics ; Mutation ; Nephrosis ; genetics

Objective: To analyze the clinical characteristics of 6 children with TTC21B-related nephronophthisis to provide reference for early clinical diagnosis. Methods: The general condition, clinical manifestations, laboratory tests and other clinical data of 6 children from 4 families diagnosed with nephronophthisis by genetic testing in Shanghai Children's Hospital from January 2015 to December 2020 were analyzed retrospectively. Results: A total of 6 children (3 males and 3 females) developed proteinuria and progressive renal dysfunction in early infancy. The onset age of proteinuria was 18 (6, 25) months. The age at the onset of renal impairment was 22 (10, 36) months. All 6 children progressed to end-stage renal disease (ESRD) within 10 (4, 65) months of onset. Five children had hypertension, 3 children with abnormal liver function, 2 children with visceral translocation and 1 child with growth retardation. The genetic results suggested that all children carried variations TTC21B gene p.C518R. Conclusions: Children with TTC21B gene p.C518R nephronophthisis had proteinuria and progressed to ESRD at the early stage of life. These nephronophthisis patients commonly presented with liver and renal dysfunction.
China ; Female ; Humans ; Kidney Diseases, Cystic/genetics* ; Kidney Failure, Chronic/genetics* ; Male ; Phenotype ; Proteinuria/genetics* ; Retrospective Studies

Erythrocytes ; metabolism ; Humans ; Kidney Diseases ; genetics ; metabolism ; Mitochondria ; genetics ; Mitochondrial Membranes ; metabolism ; Oxidative Stress ; genetics ; physiology

To study the expression of beta-human chorionic gonadotropin (beta hCG) genes in renal cell carcinomas (RCC) and benign renal disease tissues, nested reverse transcription-polymerase chain reaction (RT-PCR) and restriction endonuclease analysis were employed to detect the expression of beta hCG genes in 44 cases of RCC tissues and 24 cases of benign renal disease tissues. It was found that 52% RCC samples revealed positive for beta hCG mRNA expression. Positive rate in advanced stage and poorly differentiated RCC was higher, but there was no significant difference. The positive rate of beta hCG mRNA expression was 54% in 24 cases of benign renal tissues, including 3 cases out of 6 polycystic kidneys, 7 cases out of 13 renal atrophies, 2 cases out of 2 oncocytomas and 1 case out of 2 pyonephrotic kidneys. beta 7 was most frequently transcribed subtype gene independent on the histology. These findings suggested beta hCG gene transcription is not only involved in RCC but also in benign renal diseases.
Adult ; Biomarkers, Tumor ; Carcinoma, Renal Cell ; genetics ; metabolism ; Chorionic Gonadotropin, beta Subunit, Human ; biosynthesis ; genetics ; Humans ; Kidney ; metabolism ; Kidney Diseases ; genetics ; metabolism ; Kidney Neoplasms ; genetics ; metabolism ; Polycystic Kidney Diseases ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

The primary cilium of renal epithelia acts as a transducer of extracellular stimuli. Polycystin (PC)1 is the protein encoded by the PKD1 gene that is responsible for the most common and severe form of autosomal dominant polycystic kidney disease (ADPKD). PC1 forms a complex with PC2 via their respective carboxy-terminal tails. Both proteins are expressed in the primary cilia. Mutations in either gene affect the normal architecture of renal tubules, giving rise to ADPKD. PC1 has been proposed as a receptor that modulates calcium signals via the PC2 channel protein. The effect of PC1 dosage has been described as the rate-limiting modulator of cystic disease. Reduced levels of PC1 or disruption of the balance in PC1/PC2 level can lead to the clinical features of ADPKD, without complete inactivation. Recent data show that ADPKD resulting from inactivation of polycystins can be markedly slowed if structurally intact cilia are also disrupted at the same time. Despite the fact that no single model or mechanism from these has been able to describe exclusively the pathogenesis of cystic kidney disease, these findings suggest the existence of a novel cilia-dependent, cyst-promoting pathway that is normally repressed by polycystin function. The results enable us to rethink our current understanding of genetics and cilia signaling pathways of ADPKD.
Calcium ; Cilia* ; Genetics ; Kidney Diseases, Cystic ; Polycystic Kidney, Autosomal Dominant* ; Transducers ; TRPP Cation Channels*

Genetic Therapy ; Humans ; Kidney Diseases ; genetics ; therapy ; Kidney Transplantation ; Renal Dialysis ; Stem Cell Transplantation

Cofilin is a actin-binding protein in eukaryotic cells. It plays a role in maintaining the steady state of the internal environment through regulating actin dynamics, which contributes to the development of various kinds of diseases. In recent 20 years, cofilin has been widely attracted due to its regulatory effect on cell phenotype, gene transcription, apoptosis and inflammation in renal tissue. Cofilin plays a regulatory role in pathological changes in proteinuria diseases such as minimal change nephropathy, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy. It could be one of the diagnosis index for glomerular podocyte injury. At the same time, cofilin plays a key role in maintaining the polarity and function of proximal tubular epithelial cells and it is involved in the regulation of kidney inflammation in a variety of kidney diseases, such as renal ischemia/reperfusion injury, diabetic nephropathy, and hypertensive nephropathy reaction. In addition, cofilin plays an important role in epithelial-to-mesenchymal transition (EMT) of tumor cells and epithelial cells in various tissues, suggesting that cofilin may be involved in the regulation of peritoneal dialysis-related EMT and fibrosis. Cofilin might turn into the new diagnosis and treatment target of kidney diseases.
Cofilin 1 ; metabolism ; Glomerulosclerosis, Focal Segmental ; physiopathology ; Humans ; Kidney ; physiopathology ; Kidney Diseases ; physiopathology ; Proteinuria ; genetics ; physiopathology

In this paper, 2 cases of collagen Type Ⅲ glomerulopathy were analyzed. The clinical manifestations mainly included nephrotic syndrome, proteinuria, hypertension and renal dysfunction. One patient showed that the complement factor H-related protein 5 (CFHR5) gene was likely a disease-causing mutation. The pathological examination of renal tissues showed hyperplasia of mesangial matrix, sub-endothelial insertion, and double-track formation. Immunohistochemistry of Type III collagen was positive. Electron microscopy revealed that massive collagen fibers (40-70 nm in diameter) deposited in the mesangial matrix and basement membrane. As for the follow-up results, the normal renal function had kept steady and the proteinuria was moderate in 1 case treated with angiotensin Ⅱ receptor blocker. Due to other system disease, another case developed into acute kidney injury and then received hemodialysis. The clinical manifestations of collagen Type Ⅲ glomerulopathy was atypical, the light microscope pathological features were various, and the disease was mainly diagnosed by electron microscopy and immunohistochemistry.
Collagen Type III ; genetics ; Glomerular Mesangium ; Humans ; Kidney Diseases ; Kidney Glomerulus ; Proteinuria