ADCK4

INTRODUCTION: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of end-stage kidney disease in children, mostly associated with focal segmental glomerulosclerosis (FSGS). Advances in genomic science have enabled the identification of causative variants in 20-30% of SRNS patients. METHODS: We used whole exome sequencing to explore the genetic causes of SRNS in children. Totally, 101 patients with SRNS and 13 patients with nephrotic proteinuria and FSGS were retrospectively enrolled in our hospital between 2018 and 2022...

BACKGROUND: Kidney disease of children markedly affects their health and development. Limited clinical data of early-stage kidney disease render a tremendous challenge for the accurate diagnosis. Trio whole-exome sequencing (Trio-WES) is emerging as a first-line diagnostic strategy in pediatric kidney disease, and shows important implications for the precision medicine strategies of children with kidney disease. METHODS: Trio-WES was performed in 133 Chinese children with kidney disease and their parents...

PURPOSE OF REVIEW: During the past few years there has been an expansion in our understanding of gene fusions and translocations involved in cancer of the sinonasal tract. Here we review the downstream biologic effects, clinical characteristics, and pathologic features of these tumors. The molecular consequences and neo-antigens resulting from these chromosomal aberrations are considered and targets for current and future clinical trials discussed. RECENT FINDINGS: Several new, clinically relevant, chromosomal aberrations have been discovered and evaluated to varying degrees in sinonasal tumors including DEK::AFF2, BRD4::NUT, ADCK4::NUMBL, and ETV6::NTRK3...

Sinonasal mucosal melanoma is a rare tumor arising within the nasal cavity, paranasal sinuses, or nasopharynx (sinonasal tract). This study evaluated 90 cases diagnosed in 29 males and 61 females with median age 68 years. Most tumors involved the nasal cavity and had an epithelioid morphology. Spectrum of research techniques used in this analysis includes targeted-DNA and -RNA next-generation sequencing, Sanger sequencing, fluorescence in situ hybridization and immunohistochemistry. Sinonasal melanomas were commonly driven by RAS (38/90, 42%), especially NRAS (n = 36) mutations and rarely (4/90, 4%) displayed BRAF pathogenic variants...

This study aimed to identify the genes related to the body size of pigs by conducting genome-wide selection analysis (GWSA). We performed a GWSA scan on 50 pigs belonging to four small-bodied pig populations (Diannan small-eared pig, Bama Xiang pig, Wuzhishan pig, and Jeju black pig from South Korea) and 124 large-bodied pigs. We used the genetic parameters of the pairwise fixation index (FST ) and π ratio (case/control) to screen candidate genome regions and genes related to body size. The results revealed 47,339,509 high-quality SNPs obtained from 174 individuals, while 280 interacting candidate regions were obtained from the top 1% signal windows of both parameters, along with 187 genes (e...

Steroid-resistant nephrotic syndrome (SRNS) is one of the major causes of end-stage kidney disease (ESKD) in children and young adults. For approximately 30% of children with SRNS results from a genetic cause. In this study, genotype-phenotype correlations in a cohort of 283 pediatric patients with SRNS or early-onset NS (nephrotic syndrome presenting within the first year of life) from 23 major pediatric nephrology centers in China were analyzed. All patients were performed with next-generation sequencing and Sanger sequencing...

BACKGROUND: Mutations in the ADCK4 gene cause steroid-resistant nephrotic syndrome (NS), namely ADCK4-associated glomerulopathy. Reportedly, 38.5% of patients with ADCK4-associated glomerulopathy had end-stage renal disease (ESRD) at the time of diagnosis of ADCK4-associated glomerulopathy, requiring renal replacement therapy, such as dialysis and kidney transplantation. However, long-term NS recurrence risk of kidney transplantation in patients with ADCK4-associated glomerulopathy is unknown...

BACKGROUND: AarF domain-containing kinase 4 (ADCK4)-associated glomerulopathy is a mitochondrial nephropathy caused by mutations in the ADCK4 gene, which disrupt coenzyme Q10 biosynthesis. CASE PRESENTATION: We report the case of a 25-year-old female patient with ADCK4-associated glomerulopathy presenting with proteinuria (and with no additional systemic symptoms). A known missense substitution c.737G > A (p.S246N) and a novel frameshift c.577-600del (p.193-200del) mutation were found...

Mitochondrial cytopathies include a heterogeneous group of diseases that are characterized by impaired oxidative phosphorylation, leading to multi-organ involvement and progressive clinical deterioration. Most mitochondrial cytopathies that cause kidney symptoms are characterized by tubular defects, but glomerular, tubulointerstitial, and cystic diseases have also been described. Mitochondrial cytopathies can result from mitochondrial or nuclear DNA mutations. Early recognition of defects in the coenzyme Q10 (CoQ10 ) biosynthesis is important, as patients with primary CoQ10 deficiency may be responsive to treatment with oral CoQ10 supplementation, in contrast to most mitochondrial diseases...

AarF domain containing kinase 4 (ADCK4) is identified as a candidate gene associated with hereditary nephrotic syndrome (NS). Kruppel-like factor 5 (KLF5) is reported to promote podocyte survival by blocking the ERK/p38 MAPK pathways. Both ADCK4 and KLF5 are involved in the occurrence and development of podocyte disease, but their interaction remains unclear. Firstly, we found that the mRNA levels of ADCK4 and KLF5 decreased in NS patients, and both levels showed an obvious linear relationship. Secondly, we cloned the ADCK4 promoter region and examined its promoter activity in Hela, A549, and HEK 293 cell lines...

BACKGROUND: Herein, a 3-year-old boy presented with hidden-onset isolated proteinuria was reported. The disease was induced by COQ8B (previously termed ADCK4) compound heterozygous variants, including c.[271C > T] and c.[737G > A], which were inherited from his father and mother, respectively. CASE PRESENTATION: The patient visited our clinic due to non-nephrotic range proteinuria for 3 months, but no obvious abnormality was detected in the vital signs or laboratory test results...

Introduction: Primary coenzyme Q10 (CoQ10) deficiencies are a group of mitochondrial disorders that has proven responsiveness to replacement therapy. Mutations in enzymes involved in the biosynthesis of CoQ10 genes are associated with these deficits. The clinical presentation of this rare autosomal recessive disorder is heterogeneous and depends on the gene involved. Mutations in the COQ2, COQ6, PDSS2 , and ADCK4 genes are responsible for steroid-resistant nephrotic syndrome (SRNS), which is associated with extra-renal symptoms...

BACKGROUND Nephrotic syndrome (NS) is a common chronic kidney disease in children characterized by a group of clinical symptoms such as massive proteinuria, hypoproteinemia, high edema, and hyperlipidemia. Despite the tremendous efforts already made, the diagnosis for nephrotic syndrome still remains poor in children. MATERIAL AND METHODS The blood samples from 30 healthy children and 30 children with nephrotic syndrome were collected. The expression of H19 and ADCK4 (which are genes recently identified to play key roles in the development of nephrotic syndrome) in peripheral blood mononuclear cells (PBMCs), were detected by real-time quantitative polymerase chain reaction (RT-qPCR)...

Saccharomyces cerevisiae Coq8 is a member of the ancient UbiB atypical protein kinase family. Coq8, and its orthologs UbiB, ABC1, ADCK3, and ADCK4, are required for the biosynthesis of coenzyme Q in yeast, E. coli, A. thaliana, and humans. Each Coq8 ortholog retains nine highly conserved protein kinase-like motifs, yet its functional role in coenzyme Q biosynthesis remains mysterious. Coq8 may function as an ATPase whose activity is stimulated by coenzyme Q intermediates and phospholipids. A key yeast point mutant expressing Coq8-A197V was previously shown to result in a coenzyme Q-less, respiratory deficient phenotype...

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BACKGROUND: Mutations in ADCK4 (aarF domain containing kinase 4) generally manifest as steroid-resistant nephrotic syndrome and induce coenzyme Q10 (CoQ10 ) deficiency. However, the molecular mechanisms underlying steroid-resistant nephrotic syndrome resulting from ADCK4 mutations are not well understood, largely because the function of ADCK4 remains unknown. METHODS: To elucidate the ADCK4's function in podocytes, we generated a podocyte-specific, Adck4 -knockout mouse model and a human podocyte cell line featuring knockout of ADCK4 ...

Smoking behaviors, including amount smoked, smoking cessation, and tobacco-related diseases, are altered by the rate of nicotine clearance. Nicotine clearance can be estimated using the nicotine metabolite ratio (NMR) (ratio of 3'hydroxycotinine/cotinine), but only in current smokers. Advancing the genomics of this highly heritable biomarker of CYP2A6, the main metabolic enzyme for nicotine, will also enable investigation of never and former smokers. We performed the largest genome-wide association study (GWAS) to date of the NMR in European ancestry current smokers (n = 5185), found 1255 genome-wide significant variants, and replicated the chromosome 19 locus...

X-linked Alport syndrome (XLAS) is an inherited renal disease caused by mutations in COL4A5 gene. The c.2858G>T(p.(G953V)) in COL4A5 gene (rs78972735) has been considered pathogenic previously. However, there are conflicting interpretations of its pathogenicity recently. Here we presented 19 Chinese families, out of which 36 individuals (18 probands and 18 family members) carried the c.2858G>T(p.(G953V)) in COL4A5 gene. The clinical manifestations and genetic findings of them were analyzed. We found there were no clinical features of Alport syndrome not only in six probands with c...

OBJECTIVE: To analyze the clinical characteristics and genetic features of a family affected with isolated proteinuria. METHODS: Clinical data of the family was collected. Mutations of 191 renal disease-related genes in the proband were screened with next generation sequencing (NGS). Sanger sequencing was used to verify suspected mutations in his family members and 100 healthy controls. The impact of the mutation was predicted with online software SIFT. Frequency of the mutation was searched in databases including 1000 Genomic Project, ESP and ExAC...

Coenzyme Q10 deficiency causing gastrointestinal symptoms has not been reported. At least 15 genes are involved in CoQ10 biosynthesis, and one of the genes is AarF domain-containing kinase 4 (ADCK4). This case report first showed a patient who presented with Crohn's disease (CD) combined with ADCK4 glomerulopathy (ADCK4-GN). After approximately 2 years of infliximab treatment for CD, this patient has remained in clinical remission with no adverse effects. Moreover, two important findings were obtained: first, individuals with ADCK4-GN may present with complications, such as CD, which is a gastrointestinal disease, and infliximab may be effective for CD associated with ADCK4-GN...