Pathogenesis of Growth Failure in Rasopathies.

The RASopathies are a group of developmental genetic syndromes that are caused by germline mutations in genes encoding proteins of the Ras-Mitogen-Activated Protein kinase (RAS-MAPK) pathway. RASopathies include Noonan Syndrome (NS), Neurofibromatosis Type 1 (NF1), Noonan syndrome with multiple lentigines (NSML/LEOPARD), Costello syndrome (CS), Cardio-facio-cutaneous syndrome (CFC), capillary malformation-arteriovenous malformation syndrome (CM-AVM) and Legius Syndrome. These syndromes have many overlapping features; however, the most persistent feature common to all is the postnatal growth failure. The mechanism of growth failure in Rasopathies is highly complex and there are many proposed hypotheses including partial growth hormone insensitivity, growth hormone deficiency, neurosecretory dysfunction of growth hormone secretion, delayed puberty, poor feeding and skeletal abnormalities. Amongst these causes, the most widely accepted is partial growth hormone insensitivity due to a post-receptor signaling defect. Growth hormone therapy seems to be effective in improving height velocity in these syndromes, although the long-term effects on final height remain unproven. However, it is important to consider the potential risk of tumors and cardiomyopathy before and during growth hormone therapy.

被引量：5 发表：2019

Meeting Reports: The 25th Anniversary of the Growth Hormone Research Society Lisbon, Portugal, May 20, 2017.

被引量：- 发表：2017

In Memoriam: Ruth Illig, MD (1924-2017).

被引量：- 发表：2017

Therapeutic Genome Editing and its Potential Enhancement through CRISPR Guide RNA and Cas9 Modifications.

Genome editing with engineered nucleases is a rapidly growing field thanks to transformative technologies that allow researchers to precisely alter genomes for numerous applications including basic research, biotechnology, and human gene therapy. The genome editing process relies on creating a site-specific DNA double-strand break (DSB) by engineered nucleases and then allowing the cell's repair machinery to repair the break such that precise changes are made to the DNA sequence. The recent development of CRISPR-Cas systems as easily accessible and programmable tools for genome editing accelerates the progress towards using genome editing as a new approach to human therapeutics. Here we review how genome editing using engineered nucleases works and how using different genome editing outcomes can be used as a tool set for treating human diseases. We then review the major challenges of therapeutic genome editing and we discuss how its potential enhancement through CRISPR guide RNA and Cas9 protein modifications could resolve some of these challenges.

被引量：- 发表：2017

Autosomal Dominant Growth Hormone Deficiency (Type II).

被引量：- 发表：2015