Wnt/β-Catenin Signaling and Congenital Abnormalities of Kidney and Urinary Tract.

Background: Precise regulation of cell-cell communication is vital for cell survival and normal function during embryogenesis. The Wnt protein family, a highly conserved and extensively studied group, plays a crucial role in key cell-cell signaling events essential for development and regeneration. Congenital anomalies of the kidney and urinary tract (CAKUT) represent a leading cause of chronic kidney disease in children and young adults, and include a variety of birth abnormalities resulting from disrupted genitourinary tract development during embryonic development.

Molecular and clinical profiles of pediatric monogenic diabetes subtypes: comprehensive genetic analysis of 138 patients.

Background: Single gene variants that give rise to neonatal diabetes mellitus (NDM), maturity onset diabetes of the young (MODY) and syndromic forms of diabetes mellitus (SDM) are responsible for 3.1-4.2% of all diabetes cases.

Brain malformations and seizures by impaired chaperonin function of TRiC.

Malformations of the brain are common and vary in severity, from negligible to potentially fatal. Their causes have not been fully elucidated. Here, we report pathogenic variants in the core protein-folding machinery TRiC/CCT in individuals with brain malformations, intellectual disability, and seizures.

Research progress of the relationship between phosphoprotein phosphatases (PPPs) and neurodevelopmental disorders.

Reversible protein phosphorylation is a ubiquitous phenomenon essential for eukaryotic cellular processes. Recent advancements in research about neurodevelopmental disorders have prompted investigations into the intricate relationship between protein phosphatases, particularly phosphoprotein phosphatases (PPPs), and neurodevelopment. Notably, variants in 10 coding genes spanning four PPP family members have been implicated in neurodevelopmental disorders.

The spectrum of novel ABCB11 gene variations in children with progressive familial intrahepatic cholestasis type 2 in Pakistani cohorts.

Progressive familial intrahepatic cholestasis (PFIC) is a rare childhood manifested disease associated with impaired bile secretion with severe pruritus yellow stool, and sometimes hepatosplenomegaly. PFIC is caused by mutations in ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, SLC51A, USP53, KIF12, ZFYVE19, and MYO5B genes depending on its type. ABCB11 mutations lead to PFIC2 that encodes the bile salt export pump (BSEP).

Novel genotypes and phenotypes in Snijders Blok-Campeau syndrome caused by mutations.

Background: Snijders Blok-Campeau syndrome (SNIBCPS) is a rare genetic disorder characterized by facial abnormalities, hypotonia, macrocephaly, and global developmental delay (GDD) caused by mutations in gene. There is limited information on SNIBCPS and few studies on its pathogenic gene .

Methods: We utilized whole-exome sequencing, minigene splicing assay analysis, and construction of protein models to validate the suspected pathogenic mutation.

Compound heterozygous variants of ANKFY1 in a child with infantile-onset proteinuria and movement disorder.

The ANKFY1 gene encodes a protein that belongs to double zinc finger proteins involved in endocytosis. Only one family with steroid-resistant nephrotic syndrome has been reported carrying a homozygous variant in ANKFY1 so far. Here we describe the second case where a 13-year-old boy presented with infantile-onset proteinuria and movement disorder.

Copy number variants at 4q31.3 affecting the regulatory region of FBXW7 associated with neurodevelopmental delay.

Emerging research has demonstrated that genomic alterations disrupting topologically associated domains (TADs) and chromatin interactions underlie the pathogenic mechanisms of specific copy number variants (CNVs) in neurodevelopmental disorders. We report two patients with a de novo deletion and a duplication in chromosome 4q31, potentially causing FBX-related neurodevelopmental syndrome by affecting the regulatory region of FBXW7. High-throughput chromosome conformation capture (Hi-C) analysis using available capture data in neural progenitor cells revealed the rewiring of the TAD boundary close to FBXW7.

A novel gain-of-function STAT3 variant in infantile-onset diabetes associated with multiorgan autoimmunity.

Background: Germline gain-of-function (GOF) variants in the signal transducer and activator of transcription 3 (STAT3) gene lead to a rare inherited disorder characterized by early-onset multiorgan autoimmunity.

Methods: We described a Chinese patient with infantile-onset diabetes and multiorgan autoimmunity. The patient presented with early-onset type 1 diabetes and autoimmune hypothyroidism at 7 months.

Monogenic Causes Identified in 23.68% of Children with Steroid-Resistant Nephrotic Syndrome: A Single-Centre Study.

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.

Novel variants in the gene associated with syndromic X-linked intellectual disability.

Objective: The dysfunction of the gene can lead to X-linked intellectual disability and Raynaud-Claes syndrome (MRXSRC), characterized by severe cognitive impairment and mental disorders. This study aimed to investigate the genetic defects and clinical features of Chinese children with variants and explore the effect of mutant ClC-4 on the protein expression level and subcellular localization through experiments.

Methods: A total of 401 children with intellectual disabilities were screened for genetic variability using whole-exome sequencing (WES).

[Value of serum fibroblast growth factor 23 in diagnosis of hypophosphatemic rickets in children].

Objectives: To study the value of serum fibroblast growth factor 23 (FGF23) in the diagnosis of hypophosphatemic rickets in children.

Methods: A total of 28 children who were diagnosed with hypophosphatemic rickets in Children's Hospital of Nanjing Medical University from January 2016 to June 2021 were included as the rickets group. Forty healthy children, matched for sex and age, who attended the Department of Child Healthcare of the hospital were included as the healthy control group.

Diagnostic yield and novel candidate genes for neurodevelopmental disorders by exome sequencing in an unselected cohort with microcephaly.

Objectives: Microcephaly is caused by reduced brain volume and most usually associated with a variety of neurodevelopmental disorders (NDDs). To provide an overview of the diagnostic yield of whole exome sequencing (WES) and promote novel candidates in genetically unsolved families, we studied the clinical and genetic landscape of an unselected Chinese cohort of patients with microcephaly.

Methods: We performed WES in an unselected cohort of 103 NDDs patients with microcephaly as one of the features.

Prioritization of Monogenic Congenital Anomalies of the Kidney and Urinary Tract Candidate Genes with Existing Single-Cell Transcriptomics Data of the Human Fetal Kidney.

Introduction: Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in the first 3 decades of life. Over 40 genes have been identified as causative for isolated human CAKUT. However, many genes remain unknown, and the prioritization of potential CAKUT candidate genes is challenging.

From glucose sensing to exocytosis: takes from maturity onset diabetes of the young.

Monogenic diabetes gave us simplified models of complex molecular processes occurring within β-cells, which allowed to explore the roles of numerous proteins from single protein perspective. Constellation of characteristic phenotypic features and wide application of genetic sequencing techniques to clinical practice, made the major form of monogenic diabetes - the Maturity Onset Diabetes of the Young to be distinguishable from type 1, type 2 as well as neonatal diabetes mellitus and understanding underlying molecular events for each type of MODY contributed to the advancements of antidiabetic therapy and stem cell research tremendously. The functional analysis of MODY-causing proteins in diabetes development, not only provided better care for patients suffering from diabetes, but also enriched our comprehension regarding the universal cellular processes including transcriptional and translational regulation, behavior of ion channels and transporters, cargo trafficking, exocytosis.

Recessive CHRM5 variant as a potential cause of neurogenic bladder.

Neurogenic bladder is caused by disruption of neuronal pathways regulating bladder relaxation and contraction. In severe cases, neurogenic bladder can lead to vesicoureteral reflux, hydroureter, and chronic kidney disease. These complications overlap with manifestations of congenital anomalies of the kidney and urinary tract (CAKUT).

Compound heterozygous variants in WLS gene causes Zaki syndrome.

Biallelic Wnt ligand secretion mediator (WLS gene) variants are associated with Zaki syndrome (OMIM: #619648). Here, we report the first case with Zaki syndrome in the Chinese population. Whole-exome gene sequencing (WES) identified compound heterozygous variants in the WLS gene (c.

Case report: Expansion of phenotypic and genotypic data in -related syndrome: Report of two cases.

Biallelic variants were recently reported to cause non-syndromic microphthalmia with coloboma-9 (MCOPCB9) and microphthalmia and/or coloboma with developmental delay (MCOPS15). To date, only eight syndromic and non-syndromic microphthalmia cases with recessive variants have been reported. Herein, we report two unrelated new cases with biallelic variants in , widening the molecular and clinical spectrum.

A Potential Therapy Using Antisense Oligonucleotides to Treat Autosomal Recessive Polycystic Kidney Disease.

(1) Background: Autosomal recessive polycystic kidney disease (ARPKD) is a rare ciliopathy characterized by progressively enlarged kidneys with fusiform dilatation of the collecting ducts. Loss-of-function mutations in the gene, which encodes fibrocystin/polyductin, cause ARPKD; however, an efficient treatment method and drug for ARPKD have yet to be found. Antisense oligonucleotides (ASOs) are short special oligonucleotides which function to regulate gene expression and alter mRNA splicing.

Case report: Rare novel compound heterozygous variants presenting with hypertrophic cardiomyopathy, severe lactic acidosis and hypotonia in a Chinese infant.

Background: Mitochondrial intermediate peptidase, encoded by the gene, is involved in the processing of precursor mitochondrial proteins related to oxidative phosphorylation. Only a few studies have shown that mutations in can cause combined oxidative phosphorylation deficiency-31 (COXPD31), an autosomal recessive multisystem disorder associated with mitochondrial dysfunction. We report herein a rare case of an 8-month-old boy in China with hypertrophic cardiomyopathy (HCM), severe lactic acidosis, and hypotonia caused by novel compound heterozygous variants.

Clinical and molecular characterization of a patient with related spondyloepiphyseal dysplasia: Evidence of pathogenicity for a synonymous variant.

Background: A novel autosomal recessive skeletal dysplasia resulting from pathogenic variants in membrane-bound transcription factor peptidase, site 1 () has been recently delineated. To date, only three patients have been reported.

Methods: In this study, we reported the clinical and molecular features of a Chinese boy who was diagnosed with spondyloepiphyseal dysplasia.

A homozygous truncating ETV4 variant in a Nigerian family with congenital anomalies of the kidney and urinary tract.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most prevalent cause of chronic kidney disease that manifests in children. To date ~23 different monogenic causes have been implicated in isolated forms of human CAKUT, but the vast majority remains elusive. In a previous study, we identified a homozygous missense variant in E26 transformation-specific (ETS) Variant Transcription Factor 4 (ETV4) causing CAKUT via dysregulation of the transcriptional function of ETV4, and a resulting abrogation of GDNF/RET/ETV4 signaling pathway.