Combined Genetic and Transcriptional Study Unveils the Role of Gene Mutations in Congenital Diarrhea.

: Congenital diarrhea is persistent diarrhea that manifests during the neonatal period. Mutations in , which is crucial for triglyceride synthesis and lipid absorption in the small intestine, are causal factors for congenital diarrhea. In this study, we aimed to determine the value of tissue RNA sequencing (RNA-seq) for assisting with the clinical diagnosis of some genetic variants of uncertain significance.

Short Stature and Developmental Delay Associated With a Novel Frame-Shift Mutation in ZNF292: Case Report and Literature Review.

Pathogenic mutations in the ZNF292 gene are a significant genetic cause of Intellectual Developmental Disorder (IDD) in individuals, manifesting with a spectrum of clinical features including mild to severe intellectual impairment, speech delay, and co-occurring autism spectrum disorder (ASD). In this study, we present a novel clinical phenotype associated with a newly identified variant of ZNF292 and conduct a thorough review of relevant literature. A 4-year-old female patient displayed language developmental delays, short stature, and skeletal abnormalities.

[Cardiofaciocutaneous syndrome caused by microdeletion of chromosome 19p13.3: a case report and literature review].

This article reports a child with cardioaciocutaneous syndrome (CFCS) caused by a rare microdeletion of chromosome 19p13.3, and a literature review is conducted. The child had unusual facies, short stature, delayed mental and motor development, macrocephaly, and cardiac abnormalities.

[Clinical phenotype and genetic analysis of four cases of Epileptic encephalopathy caused by PCDH19 mutations].

Objective: To investigate the clinical phenotype and genotype features of children with Epileptic encephalopathy caused by PCDH19 mutations.

Methods: Four children with epilepsy caused by PCDH19 gene mutations who were treated at Shanghai Children's Medical Center from August 2015 to May 2024 were selected as study subjects. A retrospective study method was used to collect the clinical data of the patients.

Focusing on Rare Variants Related to Maturity-Onset Diabetes of the Young in Children.

In this study, we analysed the clinical and genetic characteristics and follow-up data of patients with maturity-onset diabetes of the young (MODY). From January 2015 to December 2022, patients with persistent hyperglycaemia suspected of having monogenic diabetes or diabetes syndrome were recruited, and next-generation sequencing (NGS) was performed at the Shanghai Children's Medical Center. Patients' clinical and laboratory findings were recorded preceding follow-ups.

A novel ARCN1 splice-site variant in a Chinese girl with central precocious puberty, intrauterine growth restriction, microcephaly, and microretrognathia.

The ARCN1 gene encodes the delta subunit of the coatomer protein complex I (COPI), which is essential for mediating protein transport from the Golgi complex to the endoplasmic reticulum. Variants in ARCN1 are associated with clinical features such as microcephaly, microretrognathia, intrauterine growth restriction, short rhizomelic stature, and developmental delays. We present a case of a patient exhibiting intrauterine growth restriction, preterm birth, microcephaly, micrognathia, and central precocious puberty.

Elucidating loss-of-function mechanisms of monoallelic EPAS1 mutations underlying congenital hypoplastic anaemia in a paediatric anaemia cohort.

HIF-2α, encoded by EPAS1, plays a dominant role in regulating erythropoietin (EPO) production, maintaining the dynamic balance of erythropoiesis. Gain-of-function mutations in EPAS1 cause erythrocytosis. However, anaemia caused by EPAS1 loss-of-function mutations has been confined to only one case report, and the underlying mechanism remains unclear.

Clinical and Genetic Profile of Chinese Children With Danon Disease: A Single-Center Retrospective Cohort Study.

Background: Danon disease (DD) is a rare X-linked dominant lysosomal storage disorder. Studies on DD pediatric patients are limited owing to the small number of cases and challenges in early detection.

Methods: We retrospectively analysed clinical and genetic data of 29 pediatric patients who visited our hospital for treatment or genetic counselling for DD from July 2014 to December 2023.

Concurrent de novo MACF1 mutation and inherited 16p13.11 microduplication in a preterm newborn with hypotonia, joint hyperlaxity and multiple congenital malformations: a case report.

Background: The MACF1 gene, found on chromosome 1p34.3, is vital for controlling cytoskeleton dynamics, cell movement, growth, and differentiation. It consists of 101 exons, spanning over 270 kb.

Molecular and phenotypic characteristics of Bardet-Biedl syndrome in Chinese patients.

Background: Bardet-Biedl syndrome (BBS) is a type of non-motile ciliopathy. To date, 26 genes have been reported to be associated with BBS. However, BBS is genetically heterogeneous, with significant clinical overlap with other ciliopathies, which complicates diagnosis.

Clinical and Molecular Characterization of a Patient with Generalized Arterial Calcification of Infancy Caused by Rare Mutation.

Generalized arterial calcification of infancy (GACI) is a rare autosomal-recessive disease characterized by extensive arterial calcification in infancy, with clinical manifestations such as arterial stenoses and heart failure. The ENPP1 inactivation mutation has been identified as a potential defect in most of the cases of GACI, while mutations in are demonstrated in patients who are genotyped as pseudoxanthoma elasticum and only limited cases of GACI are reported. Whole-exome sequencing was applied for the detection of pathogenic variants.

Bi-allelic variants in CEP295 cause Seckel-like syndrome presenting with primary microcephaly, developmental delay, intellectual disability, short stature, craniofacial and digital abnormalities.

Background: Pathogenic variants in the centrosome protein (CEP) family have been implicated in primary microcephaly, Seckel syndrome, and classical ciliopathies. However, most CEP genes remain unlinked to specific Mendelian genetic diseases in humans. We sought to explore the roles of CEP295 in human pathology.

Autosomal dominant neurodevelopmental disorders associated with gene variants in 6 pediatric patients.

Objectives: To analyze the clinical and genetic characteristics of children with autosomal dominant neurodevelopmental disorders caused by kinesin family member 1A (KIF1A) gene variation.

Methods: Clinical and genetic testing data of 6 children with gene heterozygous variation diagnosed in Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from the year 2018 to 2020 were retrospectively analyzed. Pathogenic variants were identified based on whole exome sequencing, and verified by Sanger sequencing.

Molecular and phenotypic spectrum of cardio-facio-cutaneous syndrome in Chinese patients.

Background: Cardio-facio-cutaneous (CFC) syndrome is a RASopathy subtype that presents with unique craniofacial dysmorphology, congenital heart disease, dermatologic abnormalities, growth retardation, and intellectual disability. This study describes the phenotypic spectrum of CFC in China and its association with CFC syndrome gene variants.

Results: Twenty Chinese CFC patients, aged 0.

SINE-VNTR-Alu retrotransposon insertion as a novel mutational event underlying Glanzmann thrombasthenia.

Background: Glanzmann thrombasthenia (GT) is an autosomal recessive platelet aggregation disorder caused by mutations in ITGA2B or ITGB3.

Objectives: We aimed to assess the phenotype and investigate the genetic etiology of a GT pedigree.

Methods: A patient with bleeding manifestations and mild mental retardation was enrolled.

A novel heterozygous variant of FOXJ1 in a Chinese female with primary ciliary dyskinesia and hydrocephalus: A case report and literature review.

Background: Primary ciliary dyskinesia (PCD) is a type of ciliary dyskinesia that is usually caused by autosomal recessive inheritance and can manifest as recurrent respiratory infections, bronchiectasis, infertility, laterality defects, and chronic otolaryngological disease. Although ependymal cilia, which affect the flow of cerebrospinal fluid in the central nervous system, have much in common with respiratory cilia in terms of structure and function, hydrocephalus is rarely associated with PCD. Recently, variants of Forkhead box J1 (FOXJ1) have been found to cause PCD combined with hydrocephalus in a de novo, autosomal dominant inheritance pattern.

Simultaneous quantification and pharmacokinetics of vincristine and its major metabolite M1 in Chinese pediatric ALL patients by LC-MS/MS.

Vincristine (VCR) is a vital component in numerous treatment regimens for pediatric blood cancer. VCR-induced peripheral neuropathy (VIPN) represents a type of VCR toxicity influenced by multiple factors, including age, race, genetic traits, dosage, interactions, and administration regimen. However, the dose-response relationship of VIPN remains elusive.

Germline Neurofibromin 1 mutation enhances the anti-tumour immune response and decreases juvenile myelomonocytic leukaemia tumourigenicity.

Juvenile myelomonocytic leukaemia (JMML) is an aggressive paediatric leukaemia characterized by mutations in five canonical RAS pathway genes, including the NF1 gene. JMML is driven by germline NF1 gene mutations, with additional somatic aberrations resulting in the NF1 biallelic inactivation, leading to disease progression. Germline mutations in the NF1 gene alone primarily cause benign neurofibromatosis type 1 (NF1) tumours rather than malignant JMML, yet the underlying mechanism remains unclear.

Complex clinical manifestations and new insights in RNA sequencing of children with diabetes and variants.

Background: -related disorders involve a wide range of clinical phenotypes, including diabetes mellitus and neurodegeneration. Inheritance patterns of pathogenic variants of this gene can be autosomal recessive or dominant, and differences in penetrance present challenges for accurate diagnosis and genetic counselling.

Methods: Three probands and one elder brother from three families were systematically evaluated and the clinical data of other family members were collected from the medical history.

Haplotype-specific MAPK3 expression in 16p11.2 deletion contributes to variable neurodevelopment.

Recurrent proximal 16p11.2 deletion (16p11.2del) is a risk factor for diverse neurodevelopmental disorders with incomplete penetrance and variable expressivity.

Two patients with KDM3B variants and new presentations of Diets-Jongmans syndrome.

KDM3B is located on chromosome 5q31 and encodes KDM3B, which is involved in histone demethylation and epigenetic regulation. Pathogenic KDM3B variants cause a dominantly inherited disorder presenting with intellectual disability (ID), short stature, and facial dysmorphism, named Diets-Jongmans syndrome. We describe two patients with KDM3B variants presenting with Diets-Jongmans syndrome.

Defective Joint Development and Maintenance in GDF6-Related Multiple Synostoses Syndrome.

Multiple synostoses syndromes (SYNS) are a group of rare genetic bone disorders characterized by multiple joint fusions. We previously reported an SYNS4-causing GDF6 c.1330 T > A (p.