investigation of the genetics of hematologic diseases

Conditions: Bone Marrow Failure Syndromes; Erythrocyte Disorder; Leukocyte Disorder; Hemostasis; Blood Coagulation Disorder; Sickle Cell Disease; Dyskeratosis Congenita; Diamond-Blackfan Anemia; Congenital Thrombocytopenia; Severe Congenital Neutropenia; Fanconi Anemia; Myelodysplastic Syndromes; Myeloproliferative Diseases

Summary: the purpose of this study is to collect and store samples and health information for current and future research to learn more about the causes and treatment of blood diseases. this is not a therapeutic or diagnostic protocol for clinical purposes. blood, bone marrow, hair follicles, nail clippings, urine, saliva and buccal swabs, left over tissue, as well as health information will be used to study and learn about blood diseases by using genetic and/or genomic research. in general, genetic research studies specific genes of an individual; genomic research studies the complete genetic makeup of an individual. it is not known why many people have blood diseases, because not all genes causing these diseases have been found. it is also not known why some people with the same disease are sicker than others, but this may be related to their genes. by studying the genomes in individuals with blood diseases and their family members, the investigators hope to learn more about how diseases develop and respond to treatment which may provide new and better ways to diagnose and treat blood diseases. primary objective: * establish a repository of dna and cryopreserved blood cells with linked clinical information from individuals with non-malignant blood diseases and biologically-related family members, in conjunction with the existing st. jude biorepository, to conduct genomic and functional studies to facilitate secondary objectives. secondary objectives: * utilize next generation genomic sequencing technologies to identify novel genetic alternations that associate with disease status in individuals with unexplained non-malignant blood diseases. * use genomic approaches to identify modifier genes in individuals with defined monogenic non-malignant blood diseases. * use genomic approaches to identify genetic variants associated with treatment outcomes and toxicities for individuals with non-malignant blood disease. * use single cell genomics, transcriptomics, proteomics and metabolomics to investigate biomarkers for disease progression, sickle cell disease (scd) pain events and the long-term cellular and molecular effects of hydroxyurea therapy. * using longitudinal assessment of clinical and genetic, study the long-term outcomes and evolving genetic changes in non-malignant blood diseases. exploratory objectives * determine whether analysis of select patient-derived bone marrow hematopoietic progenitor/stem (hspc) cells or induced pluripotent stem (ips) cells can recapitulate genotype-phenotype relationships and provide insight into disease mechanisms. * determine whether analysis of circulating mature blood cells and their progenitors from selected patients with suspected or proven genetic hematological disorders can recapitulate genotype-phenotype relationships and provide insight into disease mechanisms.

participants will be individuals (proband) receiving therapy or expert consultation regarding a non-malignant hematologic disorder. we propose to use genomics, transcriptomics, proteomics and metabolomic analysis coupled with family linkage studies to identify causal mutations in individuals with undefined hematologic disorders and to characterize genetic modifiers of defined monogenic blood diseases. a detailed medical history will be obtained, including demographic information for each proband. for each identified biologically related family member, a medical history questionnaire will be obtained. the family history and pedigree will be reviewed in conjunction with a geneticist/genetic counselor. the implications of genetic testing will be explained. if participants consent for future contact, this will take place annually for updates on medical and family history. all probands will provide peripheral blood samples, and probands who are undergoing a bone marrow aspirate/biopsy for clinical purposes will provide additional aspirates. biological family members will provide peripheral blood samples as a source for dna.

Eligibility criteria:
inclusion criteria: * an individual (proband) receiving therapy or expert consultation regarding a non-malignant hematologic disorder, mds or mpn. * a biologically-related individual to the identified proband to include: first, second or third degree relatives. exclusion criteria: * none

Keywords: genetics whole genome sequencing pediatrics and hematology