Counteracting the Common Shwachman-Diamond Syndrome-Causing c.258+2T>C Mutation by RNA Therapeutics and Base/Prime Editing.

Shwachman-Diamond syndrome (SDS) represents one of the most common inherited bone marrow failure syndromes and is mainly caused by gene mutations. Only supportive treatments are available, with hematopoietic cell transplantation required when marrow failure occurs. Among all causative mutations, the c.

OTC intron 4 variations mediate pathogenic splicing patterns caused by the c.386G>A mutation in humans and spf mice, and govern susceptibility to RNA-based therapies.

Background: Aberrant splicing is a common outcome in the presence of exonic or intronic variants that might hamper the intricate network of interactions defining an exon in a specific gene context. Therefore, the evaluation of the functional, and potentially pathological, role of nucleotide changes remains one of the major challenges in the modern genomic era. This aspect has also to be taken into account during the pre-clinical evaluation of innovative therapeutic approaches in animal models of human diseases.

Mesenchymal stem cells as adjuvant therapy for limb lengthening in achondroplasia.

Staged leg lengthening allows achondroplastic dwarfs to reach nearly normal height, but it takes long periods of external fixation and it can be burdened by delayed unions. Between 2009 and 2013, eight achondroplastic dwarfs showed delayed unions in the callus formation during femoral lengthening stages in our institute. We performed in-situ injections of bone marrow-derived stem cell concentrates.