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Examines the differential trophic effects of glial cell line-derived neurotrophic factor (GDNF) on dorsal root ganglias at embryonic and postnatal stages. Prototypic member of a transforming growth factor-beta subfamily; Major classes of GDNF-activated genes; Differential effects of GDNF at E14 and P14.

Newborn screening is an incredibly useful tool for the early identification of many metabolic disorders, including fatty acid oxidation (FAO) disorders. In many cases, molecular tests are necessary to reach a final diagnosis, highlighting the need for a thorough evaluation of genes implicated in FAO disorders. Using the ClinGen (Clinical Genome Resource) clinical validity framework, thirty genes were analyzed for the strength of evidence supporting their association with FAO disorders. Evidence was gathered from the literature by biocurators and presented to disease experts for review in order to assign a clinical validity classification of Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Reported Evidence. Of the gene-disease relationships evaluated, 22/30 were classified as Definitive, three as Moderate, one as Limited, three as No Reported Evidence and one as Disputed. Gene-disease relationships with a Limited, Disputed, and No Reported Evidence were found on two, six, and up to four panels out of 30 FAO disorder-specific panels, respectively, in the National Institute of Health Genetic Testing Registry, while over 70% of the genes on panels are definitively associated with an FAO disorder. These results highlight the need to systematically assess the clinical relevance of genes implicated in fatty acid oxidation disorders in order to improve the interpretation of genetic testing results and diagnosis of patients with these disorders. [ABSTRACT FROM AUTHOR]

Peroxisomal disorders are heterogeneous in nature, with phenotypic overlap that is indistinguishable without molecular testing. Newborn screening and gene sequencing for a panel of genes implicated in peroxisomal diseases are critical tools for the early and accurate detection of these disorders. It is therefore essential to evaluate the clinical validity of the genes included in sequencing panels for peroxisomal disorders. The Peroxisomal Gene Curation Expert Panel (GCEP) assessed genes frequently included on clinical peroxisomal testing panels using the Clinical Genome Resource (ClinGen) gene–disease validity curation framework and classified gene-disease relationships as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship. Subsequent to gene curation, the GCEP made recommendations to update the disease nomenclature and ontology in the Monarch Disease Ontology (Mondo) database. Thirty-six genes were assessed for the strength of evidence supporting their role in peroxisomal disease, leading to 36 gene-disease relationships, after two genes were removed for their lack of a role in peroxisomal disease and two genes were curated for two different disease entities each. Of these, 23 were classified as Definitive (64%), one as Strong (3%), eight as Moderate (23%), two as Limited (5%), and two as No known disease relationship (5%). No contradictory evidence was found to classify any relationships as Disputed or Refuted. The gene-disease relationship curations are publicly available on the ClinGen website (https://clinicalgenome.org/affiliation/40049/). The changes to peroxisomal disease nomenclature are displayed on the Mondo website (http://purl.obolibrary.org/obo/MONDO%5f0019053). The Peroxisomal GCEP-curated gene-disease relationships will inform clinical and laboratory diagnostics and enhance molecular testing and reporting. As new data will emerge, the gene-disease classifications asserted by the Peroxisomal GCEP will be re-evaluated periodically. [ABSTRACT FROM AUTHOR]

Summary: Expression of growth hormone (GH) and GH receptor (GHR) genes in the bursa of Fabricius of chickens suggests that it is an autocrine/paracrine site of GH production and action. The cellular localization of GH and GH mRNA within the bursa was the focus of this study. GH mRNA was expressed mainly in the cortex, comprised of lymphocyte progenitor cells, but was lacking in the medulla where lymphocytes mature. In contrast, more GH immunoreactivity (GH-IR) was present in the medulla than in the cortex. In non-stromal tissues, GH-IR and GH mRNA were primarily in lymphocytes, and also in macrophage-like cells and secretory dendritic cells. In stromal tissues, GH mRNA, GH and GHR were expressed in cells near the connective tissue (CT) between follicles and below the outer serosa. In contrast, GH (but not GH mRNA or GHR), was present in cells of the interfollicular epithelium (IFE), the follicle-associated epithelium (FAE) and the interstitial corticoepithelium. This mismatch may reflect dynamic temporal changes in GH translation. Co-expression of GHR-IR, GH-IR, GH mRNA and IgG was found in immature lymphoid cells near the cortex and in IgG-IR CT cells, suggesting an autocrine/paracrine role for bursal GH in B-cell differentiation. [Copyright &y& Elsevier]