RESUMO
SATB2-Associated syndrome (SAS) is an autosomal dominant, multisystemic, neurodevelopmental disorder due to alterations in SATB2 at 2q33.1. A limited number of individuals with 2q33.1 contiguous deletions encompassing SATB2 (ΔSAS) have been described in the literature. We describe 17 additional individuals with ΔSAS, review the phenotype of 33 previously published individuals with 2q33.1 deletions (n = 50, mean age = 8.5 ± 7.8 years), and provide a comprehensive comparison to individuals with other molecular mechanisms that result in SAS (non-ΔSAS). Individuals in the ΔSAS group were often underweight for age (20/41 = 49%) with a progressive decline in weight (95% CI = -2.3 to -1.1, p < 0.0001) and height (95% CI = -2.3 to -1.0, p < 0.0001) Z-score means from birth to last available measurement. ΔSAS individuals were often noted to have a broad spectrum of facial dysmorphism. A composite image of ΔSAS individuals generated by automated image analysis was distinct as compared to matched controls and non-ΔSAS individuals. We also present additional genotype-phenotype correlations for individuals in the ΔSAS group such as an increased risk for aortic root/ascending aorta dilation and primary pulmonary hypertension for those individuals with contiguous gene deletions that include COL3A1/COL5A2 and BMPR2, respectively. Based on these findings, we provide additional care recommendations for individuals with ΔSAS variants.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 2/genética , Proteínas de Ligação à Região de Interação com a Matriz/deficiência , Fatores de Transcrição/deficiência , Adulto , Criança , Pré-Escolar , Cromossomos Humanos Par 2/ultraestrutura , Colágeno Tipo III/deficiência , Colágeno Tipo III/genética , Colágeno Tipo V/deficiência , Colágeno Tipo V/genética , Nanismo/genética , Face/anormalidades , Feminino , Estudos de Associação Genética , Idade Gestacional , Humanos , Hipertensão Pulmonar/genética , Lactente , Masculino , Proteínas de Ligação à Região de Interação com a Matriz/genética , Microcefalia/genética , Fenótipo , Magreza/genética , Fatores de Transcrição/genéticaRESUMO
The advent of mesenchymal stem cell (MSC)-based therapies for clinical therapeutics has been an exciting and new innovation for the treatment of a variety of diseases associated with inflammation, tissue damage, and subsequent regeneration and repair. Application-based ability to measure MSC potency and fate of the cells post-MSC therapy are the variables that confound the use of MSCs therapeutics in human diseases. An evaluation of MSC function and applications with attention to detail in the preparation as well as quality control and quality assurance are only as good as the assays that are developed. In vivo measures of efficacy and potency require an appreciation of the overall pathophysiology of the model and standardization of outcome measures. The new concepts of how MSC's participate in the tissue regeneration and wound repair process and further, how this is impacted by estimates of efficacy and potency are important new topics. In this regard, this chapter will review some of the in vitro and in vivo assays for MSC function and activity and their application to the clinical arena.