title: Combined alpha-delta platelet storage pool deficiency is associated with mutations in GFI1B.
abstract: Combined alpha-delta platelet storage pool deficiency is characterized by the absence or reduction in the number of both alpha granules and dense bodies. This disorder can have variable severity as well as a variable inheritance pattern. We describe two patients from unrelated families with combined alpha-delta storage pool deficiency due to mutations in GFI1B, a zinc finger protein known to act as a transcriptional repressor of various genes. We demonstrate that this disease is associated with either a heterozygous mutation (de novo or familial) abrogating the binding of the zinc fingers with the promoter of its target genes, or by hypomorphic biallelic mutations in GFI1B leading to autosomal recessive inheritance.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States; Division of Genetics and Metabolism, Children's National Health System, Washington, DC, United States. Electronic address: ferreiracr@mail.nih.gov.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Ferreira
authors.affiliation: Special Coagulation Laboratory, Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, United States.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: Division of Hematology and Oncology, Department of Pediatrics, University of New Mexico, Albuquerque, NM, United States.
authors.forename: Shirley M
authors.initials: SM
authors.lastname: Abraham
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States; NIH Undiagnosed Diseases Program, NIH Common Fund, National Institutes of Health, Bethesda, MD, United States; Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States.
authors.forename: David R
authors.initials: DR
authors.lastname: Adams
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Simon
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States; NIH Undiagnosed Diseases Program, NIH Common Fund, National Institutes of Health, Bethesda, MD, United States.
authors.forename: May C
authors.initials: MC
authors.lastname: Malicdan
authors.affiliation: NIH Undiagnosed Diseases Program, NIH Common Fund, National Institutes of Health, Bethesda, MD, United States.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Markello
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States; Johns Hopkins University School of Medicine, Department of Pediatrics, McKusick-Nathans Institute of Genetic Medicine, Baltimore, MD, United States.
authors.forename: Meral
authors.initials: M
authors.lastname: Gunay-Aygun
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States; NIH Undiagnosed Diseases Program, NIH Common Fund, National Institutes of Health, Bethesda, MD, United States; Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States.
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D000293:Adolescent; D002648:Child; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010981:Platelet Storage Pool Deficiency / Q000235:genetics*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA / Q000379:methods*; D016335:Zinc Fingers
chemical_list: C111977:GFI1B protein, human; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins
keywords: Combined alpha-delta platelet storage pool deficiency; GFI1B; αδ-SPD