Untargeted metabolomics profiling of gestational diabetes mellitus: insights into early diagnosis and metabolic pathway alterations.

Introduction: Gestational Diabetes Mellitus (GDM) is a metabolic disorder marked by Q10 hyperglycemia that can negatively affect both mothers and newborns. The increasing prevalence of GDM and the limitations associated with the standard diagnostic test highlight the urgent need for early screening strategies that promote timely interventions.

Methods: This study aims to investigate the metabolic profile associated with GDM through an untargeted metabolomic analysis using mass spectrometry (MS)- based omics.

Exploiting O-GlcNAc dyshomeostasis to screen O-GlcNAc transferase intellectual disability variants.

O-GlcNAcylation is an essential protein modification catalyzed by O-GlcNAc transferase (OGT). Missense variants in OGT are linked to a novel intellectual disability syndrome known as OGT congenital disorder of glycosylation (OGT-CDG). The mechanisms by which OGT missense variants lead to this heterogeneous syndrome are not understood, and no unified method exists for dissecting pathogenic from non-pathogenic variants.

COL4A2-Related Disorder Presenting in Adulthood With Rhabdomyolysis.

The alpha 1 and 2 chains of type IV collagen, encoded by the COL4A1 (MIM 120130) and COL4A2 (MIM 120090) respectively, play essential roles in the vascular basement membranes. Pathogenic variants in COL4A1/ COL4A2 are associated with autosomal dominant cerebral angiopathies. The clinical manifestations of COL4A1/COL4A2-related disorders include: aneurysms, intracerebral hemorrhage, polymicrogyria, porencephaly, heterotopia, periventricular leukomalacia, epilepsy, and neurodevelopmental disorders.

Gender- and Age-Based Differences in Nonsyndromic Arteriopathies in Younger Adults.

Aneurysms are often associated with connective tissue disorders, but most occur sporadically and are nonsyndromic. Manifestations of these nonsyndromic arteriopathies across genders and age groups have not been discussed extensively in previous studies, especially in younger cohorts. We analyzed data from 84,496 patients in the Mayo Clinic Tapestry DNA Sequencing Study, excluding those with known vascular syndromes.

Associations Between Maternal Periconceptional Alcohol Consumption and Risk of Craniosynostosis Among Offspring, National Birth Defects Prevention Study, 1997-2011.

Background: Previous studies of maternal alcohol consumption and craniosynostosis have reported null or inverse associations. We updated a previous analysis of National Birth Defects Prevention Study (NBDPS) data to further examine associations between maternal alcohol consumption and craniosynostosis.

Methods: NBDPS was a multi-site, population-based case-control study.

Artificial intelligence powers regenerative medicine into predictive realm.

The expanding regenerative medicine toolkit is reaching a record number of lives. There is a pressing need to enhance the precision, efficiency, and effectiveness of regenerative approaches and achieve reliable outcomes. While regenerative medicine has relied on an empiric paradigm, availability of big data along with advances in informatics and artificial intelligence offer the opportunity to inform the next generation of regenerative sciences along the discovery, translation, and application pathway.

Use of Whole-Exome Sequencing and Pedigree Analysis to Identify X-linked Hypophosphatemia in Saudi Arabian Families.

Context: X-linked hypophosphatemia (XLH) is the most common form of inherited hypophosphatemic rickets (HR), caused by pathogenic variants in the gene. Genetic diagnosis of XLH facilitates early treatment optimization, especially for patients suitable for burosumab, a recombinant anti-fibroblast growth factor-23 monoclonal antibody.

Objective: This study aimed to use whole-exome sequencing (WES) and pedigree analysis to identify patients with XLH.

Clinicopathological and molecular features of claudin-18 isoform 2 expression in patients with colorectal cancer: a single-center retrospective study.

Background: Claudin-18 isoform 2 (CLDN18.2) is expressed in multiple cancers and is a promising target for antitumor therapy. However, there is limited knowledge regarding the prevalence and characteristics of CLDN18.

COL9A1-related disorder with pectus carinatum, without epiphyseal dysplasia: case report and review of literature.

COL9A1 encodes the alpha-1 chain of type IX collagen heterotrimer, which is a vital component of collagen fibrils in hyaline cartilage. There are preliminary lines of evidence suggesting that COL9A1 mutations may be associated with autosomal dominant multiple epiphyseal dysplasia (MED), a disorder affecting the epiphysis of long bones. With only 2 reported cases (both from the same family) of MED in autosomal dominant COL9A1-related disorders (MIM 614135) in the clinical scientific literature hitherto, the phenotype is poorly understood at present.

Hyperphosphatemic Familial Tumoral Calcinosis.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare, autosomal recessive condition characterized by fibroblast growth factor 23 signaling pathway dysregulation, hyperphosphatemia and ectopic calcifications (which manifest as joint motion limitations), inflammatory bony pain, and disability. Given the rarity and multiorgan involvement of HFTC, a multidisciplinary approach including Dermatology, Ophthalmology, Dentistry, Nephrology, Endocrinology, Rheumatology, and Genetics is necessary for diagnosis and treatment. We present a multidisciplinary diagnostic and treatment approach for a patient with HFTC due to a gene mutation with unique imaging highlighting the extent of calcinosis seen in HFTC.

The Complexity of Familial Inheritance in Pectus Excavatum: A Ten-Family Exome Sequencing Analysis.

: Pectus excavatum (PEx) is considered, at least partially, a familial disorder. A variety of inheritance patterns, associations with genetic syndromes, and pathogenic variants have been reported. However, the etiology of this condition is still not completely understood, and no known genes have been identified as definitive contributors.

Early separation and parallel clonal selection of dedifferentiated and well-differentiated components in dedifferentiated liposarcoma.

Dedifferentiated liposarcoma (DDLPS) comprises a high-grade dedifferentiated (DD) component and a juxtaposed well-differentiated (WD) component. The DD component is believed to originate from the WD component by acquiring additional genomic alterations. In this study, we performed multiregion genome, epigenome, and transcriptome analyses of three patients with DDLPS.

Tailor-made embryo transfer considering embryonic developmental speed to overcome the dilemma of personalized embryo transfer.

Research Question: Does tailor-made embryo transfer (TmET), timed with respect to embryonic developmental speed, affect pregnancy outcomes in patients with recurrent implantation failure?

Design: Among 741 patients identified as receptive through endometrial receptivity testing, the clinical pregnancy rates and live birth rates were retrospectively compared between those who underwent standard personalized embryo transfer and those who underwent TmET in hormone replacement therapy cycles. Personalized embryo transfer was performed according to endometrial receptivity test results (standard personalized embryo transfer group) or considering embryonic developmental speed (TmET group). For TmET, the expansion grade of warmed blastocysts was estimated based on each patient's previous embryonic developmental pattern.

O-GlcNAcylation modulates expression and abundance of N-glycosylation machinery in an inherited glycosylation disorder.

Core components of the N-glycosylation pathway are known, but the metabolic and post-translational mechanisms regulating this pathway in normal and disease states remain elusive. Using a multi-omic approach in zebrafish, we discovered a mechanism whereby O-GlcNAcylation directly impacts the expression and abundance of two rate-limiting proteins in the N-linked glycosylation pathway. We show in a model of an inherited glycosylation disorder PMM2-CDG, congenital disorders of glycosylation that phosphomannomutase deficiency is associated with increased levels of UDP-GlcNAc and protein O-GlcNAcylation.

Postprandial Metabolomic Profiling: Insights into Macronutrient-Specific Metabolic Responses in Healthy Individuals.

Background/objectives: Understanding the metabolic responses to different macronutrients is crucial for assessing their impacts on health. This study aims to investigate the postprandial metabolomic profiles of healthy individuals following the consumption of glucose, protein, and lipids.

Methods: Twenty-three healthy, normal-weight adults participated in the study, randomly assigned to consume 300 kcal from glucose, protein, or lipids after an overnight fast.

Predictive and prognostic value of excision repair cross-complementing group 1 in patients with advanced gastric cancer.

Background: To define the optimal chemotherapy regimen for each patient we therefore used tissue from patients to identify molecular prognostic or predictive biomarkers.

Methods: Endoscopic biopsy specimens from primary lesions and surgical specimens on a phase III trial in patients with unresectable advanced or recurrent gastric cancer treated with docetaxel with cisplatin plus S-1 (DCS) or cisplatin plus S-1 (CS), were collected. We measured the mRNA expression of ERCC1 and analyzed SNPs in GSTP1 and ERCC1.

A familial chromosome 4p16.3 terminal microdeletion that does not cause Wolf-Hirschhorn (4p-) syndrome.

Chromosome 4p16.3 microdeletions are known to cause Wolf-Hirschhorn syndrome (WHS), which is characterized by a distinct craniofacial gestalt and multiple congenital malformations. The 4p16.

Arab founder variants: Contributions to clinical genomics and precision medicine.

Background: Founder variants are ancestral variants shared by individuals who are not closely related. The large effect size of some of these variants in the context of Mendelian disorders offers numerous precision medicine opportunities.

Methods: Using one of the largest datasets on Mendelian disorders in the Middle East, we identified 2,908 medically relevant founder variants derived from 18,360 exomes and genomes and investigated their contribution to the clinical annotation of the human genome.

CHD2-related epilepsy with eyelid myoclonia: Report of three cases.

The aim of this study is to report three cases of epilepsy with eyelid myoclonia (EEM) with CHD2 pathogenic variants. A database of 134 patients with EEM evaluated at Mayo Clinic sites was searched to identify patients with CHD2 variants. The medical records of those identified were reviewed to describe their presentation, treatment, and clinical course.