The latest medical research on Clinical Genetics

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about clinical genetics gathered by our medical AI research bot.

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High-resolution imaging of living gut mucosa: lymphocyte clusters beneath intestinal M cells are highly dynamic structures.

Cell and Tissue Research

In the Peyer's patches of the small intestine, specialized epithelial cells, the membranous (M) cells, sample antigenic matter from the gut lumen a...

Control of cell migration by the novel protein phosphatase-2A interacting protein inka2.

Cell and Tissue Research

Cell migration is essential for many physiological and pathological processes, including embryonic development, wound healing, immune response and ...

Insights into the expression profiles and functions of circRNAs in a newborn hyperoxia-induced rat bronchopulmonary dysplasia model.

J Gene Med

Bronchopulmonary dysplasia (BPD) is a severe chronic lung disease in preterm infants. Circular RNAs (circRNAs) are key regulators of various biological processes. This study aimed to explore the biological roles of circRNAs in BPD pathogenesis.

A newborn BPD rat model was developed to construct a circRNA library; deep sequencing was used to reveal differential expression of circRNAs in the hyperoxia-induced BPD rat models. Sanger sequencing and RT-PCR were performed to confirm circRNAs that may be related to BPD. After miRNA binding-site prediction, we constructed a network diagram of circRNA-competing endogenous RNAs (ceRNAs) related to transforming growth factor-beta (TGF-beta) and p53 pathways using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.

A total of 256 differentially expressed circRNAs were detected between the hyperoxia group and the normoxia group. Of these circRNAs, 195 were up-regulated and 61 were down-regulated. The differences of circRNA distribution between the two groups were analyzed and six circRNAs were validated in the tissue samples. GO analysis indicated that 6519 target genes were enriched in cell location and biological processes. KEGG pathway enrichment analysis showed that circRNAs involved in 242 KEGG pathways. A network diagram of circRNA-ceRNA related to TGF-beta and p53 pathways was constructed.

CircRNAs are differentially expressed between the BPD model and control group. Many target genes of circRNAs are involved in the developmental process, which suggests that BPD may be associated with pathways including extracellular matrix-receptor interaction, vascular endothelial growth factor signaling, and vascular smooth muscle contraction.

RPE65 and retinal dystrophy: Report of new and recurrent mutations.

J Gene Med

Leber congenital amaurosis (LCA) is a severe and congenital or early onset form of inherited retinitis pigmentosa (RP). To date, approximately 25 genes have been introduced in relation to LCA. In this regard, retinal pigment epithelium-specific 65 kDa (RPE65) is a well-known gene mutation that plays a role in the pathogenesis of 5-10% of LCA cases.

Two individuals fromseparate families were subjected to ehole exome sequencing (WES). Causativevariants were searched further assessed using Sanger sequencing.

Here, two families with mutations in the RPE65 gene show severe and early onset LCA, as expected. In addition to the characterization of the phenotype, by reporting a new mutation (c.1451-1G>A), we further expand the mutation spectrum of RPE65. Likewise, as an interesting aspect of our study, we report on a previously reported RP-linked mutation associated with severe early onset LCA (c.T200G:p.L67R).

Considering this variant in different populations, it is likely that it represents a hotspot and affects the function of the coded protein. The variable expressivity of the phenotype can be assumed by the presence of the modifier allele(s) as a result of a different genetic background or the effect of different environments on phenotype expression.

Porcine models for studying complications and organ crosstalk in diabetes mellitus.

Cell and Tissue Research

The worldwide prevalence of diabetes mellitus and obesity is rapidly increasing not only in adults but also in children and adolescents. Diabetes i...

Interaction with ectopic cochlear crista sensory epithelium disrupts basal cochlear sensory epithelium development in Lmx1a mutant mice.

Cell and Tissue Research

The LIM homeodomain transcription factor Lmx1a shows a dynamic expression in the developing mouse ear that stabilizes in the non-sensory epithelium...

Foxn1 and Prkdc genes are important for testis function: evidence from nude and scid adult mice.

Cell and Tissue Research

Mutations in Foxn1 and Prkdc genes lead to nude and severe combined immunodeficiency (scid) phenotypes, respectively. Besides being immunodeficient...

Distinct expression patterns of aquaporin 3 and 5 in ductal and alveolar epithelial cells in mouse mammary glands before and after parturition.

Cell and Tissue Research

Milk osmolarity maintains an isotonic status for suckling infants during lactation. However, it remains unclear how the water content in milk is re...

LINC01410 promotes cell proliferation and migration of cholangiocarcinoma through modulating miR-124-3p/SMAD5 axis.

J Gene Med

Cholangiocarcinoma (CCA) is generally associated with high incidence and poor prognosis. Nowadays, increasing experimental data demonstrate that long non-coding RNA (lncRNA) plays an indispensable role in tumor occurrence. Nevertheless, the specific mechanism of lncRNA is not clear in CCA.

The relative expressions of lncRNAs, miRNAs, and mRNAs were detected by real-time quantitative PCR (RT-qPCR). CCK8 and colony formation assays were applied to examine cell proliferation ability in CCA. Transwell assay was conducted to measure the migration and invasion capabilities of CCA cells. Nuclear and cytoplasmic separation assay was implemented to figure out the location of LINC01410. Luciferase reporter assay, RIP and RNA pull-down assays were applied to certify the molecular bindings. Western blot was applied to detect the protein level.

The high expression of LINC01410 was proved in CCA tissues and CCA cell lines. Also, CCA patients with high LINC01410 level presented poor prognosis. LINC01410 deficiency impeded cell proliferation, migration and invasion in HuCCT1 and RBE cell lines. What's more, LINC01410 interacted with miR-124-3p. Meanwhile, SMAD5 targeted and inhibited by miR-124-3p. SMAD5 expression was enhanced by LINC01410.

LINC01410 facilitates cell proliferation, migration and invasion through miR-124-3p/SMAD5 axis.

Defining the clinical phenotype of Saul-Wilson syndrome.

Genet Med

Four patients with Saul-Wilson syndrome were reported between 1982 and 1994, but no additional individuals were described until 2018, when the molecular etiology of the disease was elucidated. Hence, the clinical phenotype of the disease remains poorly defined. We address this shortcoming by providing a detailed characterization of its phenotype.

Retrospective chart reviews were performed and primary radiographs assessed for all 14 individuals. Four individuals underwent detailed ophthalmologic examination by the same physician. Two individuals underwent gynecologic evaluation. Z-scores for height, weight, head circumference and body mass index were calculated at different ages.

All patients exhibited short stature, with sharp decline from the mean within the first months of life, and a final height Z-score between -4 and -8.5 standard deviations. The facial and radiographic features evolved over time. Intermittent neutropenia was frequently observed. Novel findings included elevation of liver transaminases, skeletal fragility, rod-cone dystrophy, and cystic macular changes.

Saul-Wilson syndrome presents a remarkably uniform phenotype, and the comprehensive description of our cohort allows for improved understanding of the long-term morbidity of the condition, establishment of follow-up recommendations for affected individuals, and documentation of the natural history into adulthood for comparison with treated patients, when therapeutics become available.

A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome.

Genet Med

To investigate if specific exon 38 or 39 KMT2D missense variants (MVs) cause a condition distinct from Kabuki syndrome type 1 (KS1).

Multiple individuals, with MVs in exons 38 or 39 of KMT2D that encode a highly conserved region of 54 amino acids flanked by Val3527 and Lys3583, were identified and phenotyped. Functional tests were performed to study their pathogenicity and understand the disease mechanism.

The consistent clinical features of the affected individuals, from seven unrelated families, included choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, and thyroid abnormalities. None of the individuals had intellectual disability. The frequency of clinical features, objective software-based facial analysis metrics, and genome-wide peripheral blood DNA methylation patterns in these patients were significantly different from that of KS1. Circular dichroism spectroscopy indicated that these MVs perturb KMT2D secondary structure through an increased disordered to ɑ-helical transition.

KMT2D MVs located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from KS1. Unlike KMT2D haploinsufficiency in KS1, these MVs likely result in disease through a dominant negative mechanism.

GATAD2B-associated neurodevelopmental disorder (GAND): clinical and molecular insights into a NuRD-related disorder.

Genet Med

Determination of genotypic/phenotypic features of GATAD2B-associated neurodevelopmental disorder (GAND).

Fifty GAND subjects were evaluated to determine consistent genotypic/phenotypic features. Immunoprecipitation assays utilizing in vitro transcription-translation products were used to evaluate GATAD2B missense variants' ability to interact with binding partners within the nucleosome remodeling and deacetylase (NuRD) complex.

Subjects had clinical findings that included macrocephaly, hypotonia, intellectual disability, neonatal feeding issues, polyhydramnios, apraxia of speech, epilepsy, and bicuspid aortic valves. Forty-one novel GATAD2B variants were identified with multiple variant types (nonsense, truncating frameshift, splice-site variants, deletions, and missense). Seven subjects were identified with missense variants that localized within two conserved region domains (CR1 or CR2) of the GATAD2B protein. Immunoprecipitation assays revealed several of these missense variants disrupted GATAD2B interactions with its NuRD complex binding partners.

A consistent GAND phenotype was caused by a range of genetic variants in GATAD2B that include loss-of-function and missense subtypes. Missense variants were present in conserved region domains that disrupted assembly of NuRD complex proteins. GAND's clinical phenotype had substantial clinical overlap with other disorders associated with the NuRD complex that involve CHD3 and CHD4, with clinical features of hypotonia, intellectual disability, cardiac defects, childhood apraxia of speech, and macrocephaly.