TCIRG1‐Associated Congenital Neutropenia |
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| Authors: | Audrey Anna Bolyard Merideth L Kelley Jennifer E Below Michael J Bamshad Kathryn M Bofferding Joshua D Smith Kati Buckingham Laurence A Boxer Julia Skokowa Karl Welte Deborah A Nickerson Gail P Jarvik David C Dale for the UW Center for Mendelian Genomics |
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| Institution: | 1. Department of Medicine, Divisions of GIM, University of Washington, Seattle, Washington;2. Division of Epidemiology, Human Genetics & Environmental Sciences, University of Texas School of Public Health, Houston, Texas;3. Department of Genome Sciences, University of Washington, Seattle, Washington;4. Department of Pediatrics, University of Washington, Seattle, Washington;5. Pediatric Hematology Oncology, University of Michigan, Ann Arbor, Michigan;6. Department of Molecular Hematopoiesis, Kinderklinik, Medizinische Hochschule, Hannover, Germany;7. Department of Medicine, Medical Genetics, University of Washington, Seattle, Washington |
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| Abstract: | Severe congenital neutropenia (SCN) is a rare hematopoietic disorder, with estimated incidence of 1 in 200,000 individuals of European descent, many cases of which are inherited in an autosomal dominant pattern. Despite the fact that several causal genes have been identified, the genetic basis for >30% of cases remains unknown. We report a five‐generation family segregating a novel single nucleotide variant (SNV) in TCIRG1. There is perfect cosegregation of the SNV with congenital neutropenia in this family; all 11 affected, but none of the unaffected, individuals carry this novel SNV. Western blot analysis show reduced levels of TCIRG1 protein in affected individuals, compared to healthy controls. Two unrelated patients with SCN, identified by independent investigators, are heterozygous for different, rare, highly conserved, coding variants in TCIRG1. |
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| Keywords: | TCIRG1 congenital neutropenia SCN V‐ATPase |
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