RESUMEN
Several different types of lethal short-limbed skeletal dysplasia with platyspondylia have been recognized with a different mode of inheritance. Schneckenbecken dysplasia, a very rare lethal osteochondrodysplasia, is included in these entities, with an autosomal recessive mode of inheritance. We describe 4 new Tunisian cases with clinical, radiographic and histopathological features. The fetuses were of consanguineous parents. Prenatal diagnostics of short limbs were carried out on ultrasounds at 20, 22, 23 and 28 weeks of gestation. The radiographic findings were typical, showing especially the small ilia with medial snail-like projection. The chondro-osseous histology of the 4 cases was compatible with the diagnostics demonstrating cartilage anomalies characterized by hypercellularity, hypervascularisation and chondrocytes with central large round nucleus. Schneckenbecken dysplasia should be considered when the phenotype of dwarfism and snail feature of iliac bone associated with histological finding are presented. Frozen fetal samples should be taken in order to look for candidate genes.
Asunto(s)
Osteocondrodisplasias/diagnóstico por imagen , Ultrasonografía Prenatal , Feto Abortado/diagnóstico por imagen , Feto Abortado/patología , Adulto , Consanguinidad , Femenino , Humanos , Osteocondrodisplasias/patología , Embarazo , RadiografíaRESUMEN
The brain alterations and mental retardation in Down syndrome are associated with overdosage of chromosome 21 genes. To shed light on the understanding of the molecular effect of this genetic overdosage, gene expression studies have crucial importance to quantify expression variations in Down syndrome tissues compared to normal ones. Herein, an in situ Quantitative Assessment of Gene Expression (QAGE) was used to quantify and statistically analyze, for the first time, DOPEY2 expression variations in different regions of the Down syndrome human fetal brains and to compare them to corresponding normal brains. DOPEY2, which is localized in the Down Syndrome Critical Region (DSCR) and is a candidate gene for neurological alterations in Down syndrome, showed a delimited regional and cellular expression pattern in the cortex, hippocampus and cerebellum, characterized by different transcriptional intensities in both normal and trisomic brains. DOPEY2 is overexpressed more than 50% (1.79-, 1.97- and 2.12-folds in the cortex, cerebellum and hippocampus, respectively), and showed statistically significant differences in the overexpression ratios in the three brain regions expressing DOPEY2. The demonstration of differential DOPEY2 expression and overexpression in human fetal brains suggests that this gene is submitted to a complex transcriptional control and could depend from other human chromosome 21 genes. Moreover, DOPEY2 overexpression in the brain regions, that are altered in Down syndrome patients and involved in learning and memory processes, is in agreement to the hypothesis that this gene plays a potential role in functional brain alterations and in the pathogenesis of mental retardation in Down syndrome. This new in situ QAGE approach allowed quantitative measurements of transcriptional changes and statistical evaluations of the expression and overexpression patterns of DOPEY2 at specific regions of the brain, which is a complementary approach to qRT-PCR and microarray for transcriptome study. Moreover, this approach could be a powerful tool to study the candidate chromosome 21 genes for Down syndrome and other pathologies caused by regionalized quantitative transcriptional alterations, for greater interpretation of functional processes driving gene expression.