Comprehensive genetic testing approaches as the basis for personalized management of growth disturbances: current status and perspectives

Abstract

The implementation of high-throughput and deep sequencing methods in routine genetic diagnostics has significantly improved the diagnostic yield in patient cohorts with growth disturbances and becomes increasingly important as the prerequisite of personalised medicine. They provide considerable chances to identify even rare and unexpected situations, nevertheless we must be aware of their limitations. A simple genetic test in the beginning of a testing cascade might also help to identify the genetic cause of specific growth disorders. However, the clinical picture of genetically caused growth disturbance phenotypes can vary widely, and there is a broad clinical overlap between different growth disturbance disorders. As a consequence, the clinical diagnosis and therewith connected the decision on the appropriate genetic test is often a challenge. In fact, the clinician asking for genetic testing has to weigh different aspects in this decision process, including appropriateness (single gene test, stepwise procedure, comprehensive testing), turn-around-time as the basis for a rapid intervention, and economic considerations. Therefore, a frequent question in that context is “what to test when”. In this review we aim to review genetic testing strategies and their strengthens and limitations, and to raise awareness for the future implementation of an interdisciplinary genome medicine in diagnoses, treatment and counselling of growth disturbances.

Human growth hormone and insulin, from tissue extracts to recombinant DNA technology, their biosimilars and analogues in treatment of Endocrine Disorders

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A Recombinant DNA Technique in The Genetic Engineering of Insulin from Bacteria

“…NovoNordisk have utilized the successful technology from their diabetes treatment programmes, viz using an amino acid change from Leucine to Cysteine at position 101, allowing an acylated chain to be attached as a structure which forms a non-covalent association to albumin. Human growth hormone normally is transported in plasma by a dimer of a binding protein which has lower affinity than the receptor [25].…”

First step towards a consensus strategy for multi-locus diagnostic testing of imprinting disorders

“…In the future, methodological progress in methylation specific next and third generation sequencing techniques will allow to target genome-wide genomic alterations (SNVs and CNVs) as well as epigenetic signatures in the same assay (for future perspectives see also [46]). These assays will enable the integrated analyses of genomic and epigenetic data, and in combination with additional omic techniques, the causes of disturbed imprinting and their functional consequences will be determined.…”