Project description:Long-Term Outcome in Offspring and Mothers of Dexamethasone-Treated Pregnancies at Risk for Classical Congenital Adrenal Hyperplasia Owing to 21-Hydroxylase Deficiency - GSD 5610

| PRJNA377385 | ENA

POR polymorphisms are associated with 21 hydroxylase deficiency.

Project description:PurposeGenotype-phenotype correlation in congenital 21 hydroxylase deficiency is strong but by no means absolute. Indeed, clinical and hormonal features may vary among patients carrying similar CYP21A2 mutations, suggesting that modifier genes may contribute to the phenotype. Aim of the present study was to evaluate whether polymorphisms in the p450 oxidoreductase (POR) gene may affect clinical features in patients with 21 hydroxylase deficiency METHODS: Sequencing of the POR gene was performed in 96 patients with 21 hydroxylase deficiency (49 classic, 47 non-classic) and 43 control subjects.ResultsPrevalence of POR polymorphisms in patients with 21 hydroxylase was comparable to controls and known databases. The rs2228104 polymorphism was more frequently associated with non-classic vs classic 21 hydroxylase deficiency (allelic risk 7.09; 95% C.I. 1.4-29.5, p < 0.05). Classic 21 hydroxylase-deficient carriers of the minor allele in the rs2286822/rs2286823 haplotype presented more frequently the salt-wasting form (allelic risk 1.375; 95% C.I. 1.138-1.137), more severe Prader stage at birth (allelic risk 3.85; 95% C.I. 3.78-3.92), higher ACTH levels, and younger age at diagnosis.ConclusionsPolymorphisms in the POR gene are associated with clinical features of 21 hydroxylase deficiency both as regards predisposition to classic vs non-classic forms and severity of classic adrenal hyperplasia.

| S-EPMC8421294 | biostudies-literature

Molecular Diagnosis of Steroid 21-Hydroxylase Deficiency: A Practical Approach.

Project description:Adrenal insufficiency in paediatric patients is mostly due to congenital adrenal hyperplasia (CAH), a severe monogenic disease caused by steroid 21-hydroxylase deficiency (21-OHD, encoded by the CYP21A2 gene) in 95% of cases. CYP21A2 genotyping requires careful analyses that guaranty gene-specific PCR, accurate definition of pseudogene-gene chimeras, gene duplications and allele dropout avoidance. A small panel of well-established disease-causing alterations enables a high diagnostic yield in confirming/discarding the disorder not only in symptomatic patients but also in those asymptomatic with borderline/positive results of 17-hydroxyprogesterone. Unfortunately, the complexity of this locus makes it today reluctant to high throughput techniques of massive sequencing. The strong relationship existing between the molecular alterations and the degree of enzymatic deficiency has allowed genetic studies to demonstrate its usefulness in predicting/classifying the clinical form of the disease. Other aspects of interest regarding molecular studies include its independence of physiological variations and analytical interferences, its usefulness in the diagnosis of simple virilizing forms in males and its inherent contribution to the genetic counseling, an aspect of great importance taking into account the high carrier frequency of CAH in the general population. Genetic testing of CYP21A2 constitutes an irreplaceable tool to detect severe alleles not just in family members of classical forms but also in mild late-onset forms of the disease and couples. It is also helpful in areas such as assisted reproduction and preimplantation diagnosis. Molecular diagnosis of 21-OHD under expert knowledge definitely contributes to a better management of the disease in every step of the clinical course.

| S-EPMC9001848 | biostudies-literature

Lysyl hydroxylase 2 deficiency promotes filopodia formation and fibroblast migration

Project description:Lysyl hydroxylase 2 (LH2) regulates the intermolecular cross-linking of collagen molecules. Accumulation of LH2-modified collagen, which is highly stable and resistant to collagenase cleavage, is one of the causes of fibrosis. In this study, we established LH2-deficient fibroblasts and first analyzed morphology of LH2-deficient fibroblasts by microscopy. LH2-deficient fibroblasts showed a dramatic increase in filopodial dynamics and cell migration, which were supported by time-lapse video microscopy and Immunocytochemistry, and gene expression profiling data. Understanding the precise role of phenotype in LH2-deficient cells may be helpful to define the pathogenesis of fibrosis.

2021-10-20 | GSE186100 | GEO

Lysyl hydroxylase 2 deficiency promotes filopodia formation and fibroblast migration

Project description:Lysyl hydroxylase 2 deficiency promotes filopodia formation and fibroblast migration

| PRJNA772615 | ENA

Lung Megakaryocytes are Immune Modulatory Cells

Project description:Lung Megakaryocytes are Immune Modulatory Cells

| PRJNA664993 | ENA