Kabuki Syndrome

Myelodysplastic syndromes (MDS) are chronic blood disorders marked by ineffective blood cell production and normal marrow richness. This research aims to understand the biological and clinical aspects of MDS, including its progression to acute leukemia, which occurs in 30 to 40% of cases. The study focuses on the genetic and molecular diversity of MDS and seeks to identify markers predicting disease progression through a biocollection. The study involves collecting and analyzing biological material from patients diagnosed or suspected of having MDS. It explores three key scientific projects: splicing abnormalities related to SF3B1 mutations, the role of chromosomal deletions such as 5q affecting splicing genes RBM22 and SLU7, and the progression of MDS to acute myeloid leukemia by studying the clonal architecture of malignant cells. These projects use advanced genetic and molecular analysis techniques to deepen understanding of MDS mechanisms. Participants provide biological samples and clinical data, which are used for detailed genetic and functional studies. The study monitors patients over time to observe disease evolution and identify prognostic markers. The primary outcome is an epidemiologic study of the MDS patient cohort over five years. Participation includes consenting to data and sample collection, enabling researchers to analyze molecular changes and better understand MDS progression and prognosis.

Researchers are evaluating a phase II, open-label study of T cell receptor alpha/beta depletion (TCR α/β TCD) peripheral blood stem cell transplantation for children and adults with blood cancers, including acute leukemias and myelodysplasia. This study focuses on the safety and feasibility of this investigational transplantation approach in patients up to 60 years old. Participants receive treatment based on the most medically appropriate regimen, with a preference for regimens including Fludarabine, Total Body Irradiation, Busulfan, Melphalan, Antithymocyte Globulin, and Cyclophosphamide. On Day 0, patients receive an infusion of alpha/beta T cell-depleted hematopoietic stem cells. Several conditioning regimens are used depending on patient characteristics, including specialized approaches for pediatric patients and those with juvenile myelomonocytic leukemia or infant leukemia. During the study, participants are monitored for outcomes such as graft-versus-host disease within 100 days, transplant engraftment by 42 days, graft failure by 100 days, and overall survival over 12 months. Safety and organ function are assessed, and patients receive medications including Rituximab and Levetiracetam to reduce risks. The trial is sponsored by the Masonic Cancer Center at the University of Minnesota and continues until November 2030.

Researchers are conducting a patient registry and natural history study called Coordination of Rare Diseases at Sanford (CoRDS) to support research on rare diseases. CoRDS is an international registry that connects patients with rare, undiagnosed, or uncommon diseases to researchers studying over 7,000 rare diseases. This program aims to help advance treatments and cures by facilitating easy collaboration between patients, advocacy groups, and researchers. It is based at Sanford Research in Sioux Falls, South Dakota, and is free for patients to join and for researchers to access. Participants provide contact, sociodemographic, and health information, which is entered into CoRDS and linked to a unique coded identifier. Examples of collected data include name, mailing address, phone number, email, date and place of birth, sex, gender, ethnicity, family history, and diagnosis-related information. De-identified information may be shared with approved researchers after review by an Institutional Review Board and expert panel. Some data may also be shared with other databases and patient advocacy groups, with protections to prevent misuse for research purposes. Participants are contacted yearly to confirm continued participation and to update their information. If a parent or legal guardian consents for a minor, the participant will be contacted at age 18 to provide their own consent. The primary goal is to accelerate research by connecting individuals interested in rare disease research with scientists over a long period of up to 100 years. There is no treatment given, as this is an observational registry study.