Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey

Purpose: Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases. Methods: We compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic ACP5 mutations. Results: We observed a variability in skeletal, neurological and immune phenotypes, which was sometimes marked even between affected siblings. In total, 22 of 26 patients manifested autoimmune disease, most frequently autoimmune thrombocytopenia and systemic lupus erythematosus. Four patients were considered to demonstrate no clinical autoimmune disease, although two were positive for autoantibodies. In the majority of patients tested we detected upregulated expression of interferon-stimulated genes (ISGs), in keeping with the autoimmune phenotype and the likely immune-regulatory function of the deficient protein tartrate resistant acid phosphatase (TRAP). Two mutation positive patients did not demonstrate an upregulation of ISGs, including one patient with significant autoimmune disease controlled by immunosuppressive therapy. Conclusions: Our data expand the known phenotype of SPENCD. We propose that the OMIM differentiation between spondyloenchondrodysplasia and spondyloenchondrodysplasia with immune dysregulation is no longer appropriate, since the molecular evidence that we provide suggests that these phenotypes represent a continuum of the same disorder. In addition, the absence of an interferon signature following immunomodulatory treatments in a patient with significant autoimmune disease may indicate a therapeutic response important for the immune manifestations of spondyloenchondrodysplasia

A comparative study of cDNA microarray analysis of familial and sporadic breast cancer in India

Many genes and signalling pathways controlling cell proliferation, death and differentiation, as well as genomic integrity, are involved in cancer development. Techniques, such as cDNA microarrays, have enabled measurement of the expression of thousands of genes in a single experiment, revealing many new, potentially important cancer genes. Human breast cancer is usually caused by genetic alterations of somatic cells of the breast, but occasionally, susceptibility to the disease is inherited. As a step towards understanding the differences between familial and sporadic breast cancer in humans, gene expression patterns were examined in breast tumours. Sporadic (n = 7) and familial (n = 6) tissue samples, and normal breast tissue (n = 3) samples, were collected from women who underwent breast surgery at Karnataka Cancer Therapy and Research Institute (KCTRI), Hubli. Total RNA was isolated and subjected to cDNA microarray for 14,992 genes on Agilent’s Human 8x15K Array. Gene expression profiles were analysed using Genespring software. F-Test was carried out to find the variance in terms of gene expression patterns between familial and sporadic breast cancer tissue samples. Our study revealed, that, there is no significant variation between sporadic and familial breast cancer in terms of gene expression profiles. With this, it can be concluded that both familial and sporadic breast cancers are similar in terms of the gene expression profiles. This will guide in development of common biomarkers for both familial and sporadic breast cancer and will also help in diagnosis, prognosis and treatment

Erratum to: Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey

status: publishe

Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey

Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases.status: publishe