Atp6v0a2

BACKGROUND: Cutis laxa is a connective tissue disease caused by abnormal synthesis or secretion of skin elastic fibers, leading to skin flabby and saggy in various body parts. It can be divided into congenital cutis laxa and acquired cutis laxa, and inherited cutis laxa syndromes is more common in clinic. METHODS: In this study, we reported a case of a Han-Chinese male newborn with ATP6V0A2 gene variant leading to cutis laxa. The proband was identified by whole-exome sequencing to determine the novel variant, and their parents were verified by Sanger sequencing...

Extracellular vesicles (EVs) are bilayered membrane vesicles produced by living cells and secreted into the extracellular matrix. Bile is a special body fluid that is secreted by the liver cells, and extracellular vesicles long RNAs (exLRs) has not been explored in bile. In this study, exLR sequencing (exLR-seq) was performed on 19 bile samples from patients with malignant cancer or patients with biliary stones. A total of 8649 mRNAs, 13823 circRNAs and 1105 lncRNAs were detected. The KEGG pathway analysis revealed that differentially expressed exLRs were enriched in mTOR and AMPK signaling pathway...

BACKGROUND AND AIMS: The important role of extracellular vesicles (EVs) in liver fibrosis has been confirmed. However, EVs derived from liver sinusoidal endothelial cells (LSECs) in the activation of hepatic stellate cells (HSCs) and liver fibrosis is still unclear. Our previous work demonstrated that Aldosterone (Aldo) may have the potential to regulate EVs from LSECs via autophagy pathway. Thus, we aim to investigate the role of Aldo in the regulation of EVs derived from LSECs. APPROACH AND RESULTS: Using an Aldo-continuous pumping rat model, we observed that Aldo-induced liver fibrosis and capillarization of LSECs...

BACKGROUND: Autosomal recessive cutis laxa type 2A (ARCL2A; OMIM: 219200) is characterized by neurovegetative, developmental and progeroid elastic skin anomalies. It is caused by biallelic variation in ATPase, H+ transporting V0 subunit A2 (ATP6V0A2; OMIM: 611716) located on chromosome 12q24.31. Autosomal recessive cutis laxa type 3A (ARCL3A; OMIM: 219150) is another subclinical type characterized by short stature, ophthalmological abnormalities and a progeria-like appearance. The ARCL3A is caused by loss of function alterations in the aldehyde dehydrogenase 18 family member A1 (ALDH18A1; OMIM: 138250) gene located at chromosome 10q24...

PURPOSE: To report a case of Autosomal recessive Cutis Laxa type 2A with novel retinal findings. METHODS: Case Report. RESULTS: 22-year-old female patient presented with a longstanding history of reduced visual acuity in her right eye. She has generalized redundant skin, downslanting of palpebral fissures, and long philtrum. Ophthalmic examination showed ptosis in her right eye and visual acuity of 20/2000 in the right eye and 20/30p in the left eye...

Cutis laxa (CL) can be caused by mutations in a number of genes. Cutis laxa with autosomal recessive inheritance due to mutations in several genes, including mutations in the ATP6V0A2 gene, causes autosomal recessive cutis laxa type 2A (ARCL2A). The ATP6V0A2 gene encodes the a2 subunit in the V-ATPases pump. The V-ATPases are located in the membrane of some organelles, including the Golgi or some vesicles, and act as ATP-dependent proton pumps to pH adjustment intracellular segments. Mutations in the ATP6V0A2 gene consist present in ARCL2A patients...

OBJECTIVE: To explore the clinical characteristics and genetic basis for a child featuring autosomal recessive cutis laxa (ARCL). METHODS: Clinical data of the patient was collected. Trio-whole exome sequencing (trio-WES) was carried out for the proband, his sister and parents. Candidate variant was verified by Sanger sequencing. RESULTS: The 5 years and 2 month old child, was 109.5 cm tall (40% centile) and 14.2 kg in weight (< 3% centile)...

Congenital disorders of glycosylation (CDG) are inherited metabolic diseases that affect the synthesis of glycoconjugates. Defects in mucin-type O -glycosylation occur independently or in combination with N -glycosylation disorders, and the profiling of the O -glycans of apolipoprotein CIII (apoCIII) by mass spectrometry (MS) can be used to support a diagnosis. The biomarkers are site occupancy and sialylation levels, which are indicated by the content of non-glycosylated apoCIII0a isoform and by the ratio of monosialylated apoCIII1 to disialylated apoCIII2 isoforms, respectively...

PHY34 is a synthetic small molecule, inspired by a compound naturally occurring in tropical plants of the Phyllanthus genus. PHY34 was developed to have potent in vitro and in vivo anticancer activity against high grade serous ovarian cancer (HGSOC) cells. Mechanistically, PHY34 induced apoptosis in ovarian cancer cells by late-stage autophagy inhibition. Furthermore, PHY34 significantly reduced tumor burden in a xenograft model of ovarian cancer. In order to identify its molecular target/s, we undertook an unbiased approach utilizing mass spectrometry-based chemoproteomics...

Cutis laxa (CL) syndromes are a large and heterogeneous group of rare connective tissue disorders that share loose redundant skin as a hallmark clinical feature, which reflects dermal elastic fiber fragmentation. Both acquired and congenital-Mendelian- forms exist. Acquired forms are progressive and often preceded by inflammatory triggers in the skin, but may show systemic elastolysis. Mendelian forms are often pleiotropic in nature and classified upon systemic manifestations and mode of inheritance. Though impaired elastogenesis is a common denominator in all Mendelian forms of CL, the underlying gene defects are diverse and affect structural components of the elastic fiber or impair metabolic pathways interfering with cellular trafficking, proline synthesis, or mitochondrial functioning...

We identified three cases of congenital disorders of glycosylation (CDG) with Golgi homeostasis disruption, one ATP6V0A2-CDG and two COG4-CDG, with false-negative transferrin screening analyses. Patient 1 (P1) presented at birth with cutis laxa. Patient 2 (P2) and patient 3 (P3) are adult siblings and presented with severe symptoms evocative of inborn errors of metabolism. Targeted gene sequencing in P1 revealed pathogenic ATP6V0A2 variants, shared by her affected older brother. In P2 and P3, whole exome sequencing revealed a homozygous COG4 variant of unknown significance...

BACKGROUND: Congenital disorders of glycosylation (CDG) result from defects in the synthesis of glycans and the attachment of glycans to proteins and lipids. Our study aimed to describe the clinical, biochemical, and molecular findings of CDG patients, and to present the long-term follow-up. MATERIAL AND METHODS: A single-center study (1995-2019 years) of patients with congenital disorders of N-glycosylation and combined N- and O-hypoglycosylation was performed...

ATP6V0A2-related cutis laxa, also known as autosomal recessive cutis laxa type 2A (ARCL2A), is a subtype of hereditary cutis laxa originally characterized by skin, skeletal, and neurological involvement, and a combined defect of N-glycosylation and O-glycosylation. The associated clinical spectrum subsequently expanded to a less severe phenotype dominated by cutaneous involvement. At the moment, ARCL2A was described in a few case reports and series only. An Italian adult woman ARCL2A with a phenotype restricted to skin and the two novel c...

OBJECTIVE: To describe the clinical, biochemical, and genetic features of both new and previously reported patients with congenital disorders of glycosylation (CDG) diagnosed in Portugal over the last 20 years. STUDY DESIGN: The cohort includes patients with an unexplained multisystem or single organ involvement, with or without psychomotor disability. Serum sialotransferrin isoforms and, whenever necessary, apolipoprotein CIII (ApoC3) isoforms and glycan structures were analyzed...

Bikunin (Bkn) isoforms are serum chondroitin sulfate proteoglycans synthesized by the liver. They include two light forms, that is, the Bkn core protein and the Bkn linked to the CS chain (UTI), and two heavy forms, that is, PαI and ITI, corresponding to UTI esterified by one or two heavy chains (HC) glycoproteins, respectively. We previously showed that the Western-blot analysis of the light forms could allow the fast and easy detection of patients with linkeropathy, deficient in enzymes involved in the synthesis of the initial common tetrasaccharide linker of glycosaminoglycans...

Congenital disorders of glycosylation (CDG) are caused by defects in various genes governing glycoconjugate biosynthesis. Several responsible genes have been identified in the protein N-glycosylation process. Analyses of mucin-type core-1 O-glycoform of apolipoprotein C-III (apoCIII) have recently revealed combined N- and O-glycosylation defects. We applied matrix-assisted laser desorption/ionization mass spectrometry profiling of apoCIII glycoforms to 500 serum samples for CDG screening, and reference values were determined...

Congenital disorders of glycosylation (CDG), an increasingly recognized group of diseases that affect glycosylation, comprise the largest known subgroup of approximately 100 responsible genes related to N -glycosylation. This subgroup presents various molecular abnormalities, of either the CDG-I or the CDG-II type, attributable to a lack of glycans or abnormal glycoform profiles, respectively. The most effective approach to identifying these N -glycosylation disorders is mass spectrometry (MS) using either released glycans, intact glycoproteins or proteolytic peptides as analytes...

Vitamin D3/Calcitriol supplementation in humans is associated with reduced incidence and severity during influenza A virus (IAV) infection. Apoptosis in response to IAV infection is a major contributor to host cell death and tissue damage; however, its modulation by Vitamin D3 remains unclear. In this study, we demonstrate the efficacy of Vitamin D3 in preventing apoptosis induction by pandemic influenza A (H1N1)pdm09 virus in human alveolar cells (A549). Human alveolar epithelial cell line A549 was used to assess the cytotoxic effects of IAV infection...

BACKGROUND: There is a high prevalence of hypermobility spectrum disorder (HSD) in dancers. While there is no known genetic variant for HSD, hypermobile Ehlers-Danlos syndrome is a genetic disorder that exists within HSD. There are many connective tissue disorders (CTDs) with known (and unknown) genes associated with hypermobility. Hypermobility has distinct advantages for participation in flexibility sports, including ballet. PURPOSE: To determine the prevalence of gene variants associated with hypermobility in a large professional ballet company...

The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment. They affect multiple organ/systems but non-specific symptoms render the diagnosis of the different CDG very challenging. PMM2-CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought. The present work reports the clinical and mutational spectrum of 25 non-PMM2 CDG patients. The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%)...