Characterization of Novel PHEX Variants in X-linked Hypophosphatemic Rickets and Genotype-PHEX Activity Correlation.

Background: X-linked hypophosphatemia (XLHR) is the most common genetic form of hypophosphatemic rickets (HR), which is caused by phosphate regulating endopeptidase homolog X-linked (PHEX) gene mutation. At present, the genotype-phenotype relationship of XLHR and the pathogenic role of PHEX are not fully understood.

Methods: In this study, we summarized clinical features in a new cohort of 49 HR patients and detected 16 novel PHEX and 5 novel non-PHEX variants.

The health-care utilization and economic burden in patients with genetic skeletal disorders.

Background: Most genetic skeletal disorders (GSD) were complex, disabling and life-threatening without effective diagnostic and treatment methods. However, its impacts on health system have not been well studied. The study aimed to systematically evaluate the health-care utilization and economic burden in GSD patients.

Protein-centric omics analysis reveals circulating complements linked to non-viral liver diseases as potential therapeutic targets.

Background/aims: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets.

Methods: We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options.

Pathogenic mechanisms of osteogenesis imperfecta, evidence for classification.

Osteogenesis imperfecta (OI) is a connective tissue disorder affecting the skeleton and other organs, which has multiple genetic patterns, numerous causative genes, and complex pathogenic mechanisms. The previous classifications lack structure and scientific basis and have poor applicability. In this paper, we summarize and sort out the pathogenic mechanisms of OI, and analyze the molecular pathogenic mechanisms of OI from the perspectives of type I collagen defects(synthesis defects, processing defects, post-translational modification defects, folding and cross-linking defects), bone mineralization disorders, osteoblast differentiation and functional defects respectively, and also generalize several new untyped OI-causing genes and their pathogenic mechanisms, intending to provide the evidence of classification and a scientific basis for the precise diagnosis and treatment of OI.

Identification and characterization of novel carboxyl ester lipase gene variants in patients with different subtypes of diabetes.

Introduction: Mutations of gene were first reported to cause a new type of maturity-onset diabetes of the young (MODY) denoted as MODY8 and then were also found in patients with type 1 (T1D) and type 2 diabetes (T2D). However, its genotype-phenotype relationship has not been fully determined and how carboxyl ester lipase (CEL) variants result in diabetes remains unclear. The aim of our study was to identify pathogenic variants of in patients with diabetes and confirm their pathogenicity.

Research on the variants of FGFR1 and CEP290 genes in idiopathic hypogonadotropin hypogonadism.

Idiopathic hypogonadotropic hypogonadism (IHH) is a rare endocrine disease characterized by gonadal dysplasia. According to whether the sense of smell is affected, this disorder is classified into Kallmann syndrome (KS) and normosmic isolated hypogonadotropic hypogonadism (nIHH). In this study, we reported a case of nIHH patient and explored the pathogenic mechanism of FGFR1 in nIHH.

R158Q and G212S, novel pathogenic compound heterozygous variants in SLC12A3 of Gitelman syndrome.

The dysfunction of Na-Cl cotransporter (NCC) caused by mutations in solute carrier family12, member 3 gene (SLC12A3) primarily causes Gitelman syndrome (GS). In identifying the pathogenicity of R158Q and G212S variants of SLC12A3, we evaluated the pathogenicity by bioinformatic, expression, and localization analysis of two variants from a patient in our cohort. The prediction of mutant protein showed that p.

Identification and Functional Characterization of a Novel Variant in the Gene in a Chinese Family with Kallmann Syndrome.

Background: Kallmann syndrome (KS) is a rare genetic disease characterized by the reproductive system and olfactory dysplasia due to the defective migration of gonadotropin-releasing hormone (GnRH) neurons. However, this disorder is clinically heterogeneous and the genotype-phenotype relationship has not been determined.

Objective: The present study aimed to identify the variant causing KS in a Chinese family and evaluate the functional consequences and phenotypes associated with the novel variant.

Cell-Dependent Pathogenic Roles of Filamin B in Different Skeletal Malformations.

Mutations of filamin B () gene can lead to a spectrum of autosomal skeletal malformations including spondylocarpotarsal syndrome (SCT), Larsen syndrome (LRS), type I atelosteogenesis (AO1), type III atelosteogenesis (AO3), and boomerang dysplasia (BD). Among them, LRS is milder while BD causes a more severe phenotype. However, the molecular mechanism underlying the differences in clinical phenotypes of different variants has not been fully determined.

Characterization of a novel COL10A1 variant associated with Schmid-type metaphyseal chondrodysplasia and a literature review.

Background: Schmid-type metaphyseal chondrodysplasia (SMCD) is a rare autosomal dominant skeletal dysplasia caused by heterozygous mutations in COL10A1, the gene which encodes collagen type X alpha 1 chain. However, its genotype-phenotype relationship has not been fully determined. Subjects and Methods The proband is a 2-year-old boy, born of non-consanguineous Chinese parents.

Posttranslational Modification Defects in Fibroblast Growth Factor Receptor 1 as a Reason for Normosmic Isolated Hypogonadotropic Hypogonadism.

Some mutations in affect the sense of smell while others do not, resulting in Kallmann syndrome (KS) and normosmic isolated hypogonadotropic hypogonadism (nIHH), respectively. The underlying mechanism is still unclear. variants are found in less than 10% of patients with KS and nIHH, and among them, only some have undergone functional analysis.

TSH promotes adiposity by inhibiting the browning of white fat.

Adiposity is caused by an imbalance between energy intake and consumption. Promotion of the browning of white fat increases energy expenditure and could combat adiposity. Thyroid-stimulating hormone (TSH) has been confirmed to positively correlate with adiposity.

Molecular cloning and functional analysis of squalene synthase (SS) in Panax notoginseng.

Panax notoginseng (Burk.) F. H.

Review on the effect of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors for the treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease and it represents the hepatic manifestation of metabolic syndrome, which includes type 2 diabetes mellitus (T2DM), dyslipidemia, central obesity and hypertension. Glucagon-like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors were widely used to treat T2DM. These agents improve glycemic control, promote weight loss and improve lipid metabolism.