Publications by authors named "M H Tusseau"
Retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and migraine headache (ROSAH) syndrome is an autosomal dominant disorder and to date is known to be caused by either the Thr237Met or Tyr254Cys variant in the protein kinase ALPK1. Here, we identify a family in which ROSAH syndrome is caused by a novel variant in which Ser277 is changed to Phe. All six patients examined display ocular inflammation and optic nerve elevation, four have retinal degeneration and four are registered blind.
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- Researchers studied mutations in a gene that affects a key protein involved in cell signaling, which is linked to severe health issues like impaired immunity in patients.
- The mutations were found to disrupt normal cell behavior by promoting excessive cell growth and responses to immune signals, specifically T cell receptor stimulation.
- The mutant protein was shown to interfere with a regulatory protein, leading to heightened activity of important signaling pathways that contribute to cell growth and survival.
An exome sequencing strategy employed to identify pathogenic variants in patients with pediatric-onset systemic lupus or Evans syndrome resulted in the discovery of six novel monoallelic mutations in PTPN2. PTPN2 is a phosphatase that acts as an essential negative regulator of the JAK/STAT pathways. All mutations led to a loss of PTPN2 regulatory function as evidenced by in vitro assays and by hyperproliferation of patients' T cells.
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- - Systemic lupus erythematosus (SLE) is a complex autoimmune disease with various signs and causes, but recent discoveries of rare monogenic forms have identified specific genetic defects that contribute to its development.
- - These monogenic forms can be categorized by different signaling pathways involved in immune responses, such as those related to apoptotic cell clearance and type I interferon signaling, providing a deeper understanding of the disease's mechanisms.
- - In children, where these genetic forms are more common, genetic testing is crucial, offering about a 10% diagnostic success rate and leading to more targeted and effective treatment options based on individual genetic profiles.
Article Synopsis
- DNA-PKcs is crucial for repairing DNA double-strand breaks and is linked to a rare immunodeficiency in humans, with few documented cases compared to the well-studied Scid mouse model.
- Seven patients with mutations in the PRKDC gene showed severe combined immunodeficiency symptoms, including granulomas and autoimmunity, highlighting a predominantly inflammatory clinical picture.
- Hematopoietic stem cell transplantation has proven effective for many, leading to meaningful recovery of T- and B-cell functions in the long-term follow-up of most patients.