Hermansky-Pudlak syndrome with early onset inflammatory bowel disease due to loss of dysbindin expression |
| |
| Affiliation: | 1. Department of Pediatrics, Pediatric Immunology and Rheumatology Unit, Aster CMI Hospital, Bengaluru, India;2. Vanderbilt University School of Medicine, Nashville, TN, USA;3. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA;4. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA;5. Vanderbilt Center for Immunobiology, Vanderbilt Genetics Institute, Vanderbilt Institute for Infection Immunity and Inflammation, Nashville, TN, USA;1. Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, 9112001, Israel;2. Department of Genetics, Hadassah Medical Organization, Jerusalem, 9112001, Israel;3. University of Groningen, University Medical Centre Groningen, Dept Genetics, Groningen, Netherlands;1. VASCERN PPL European Reference Centre: Expert Center for Lymphovascular Medicine, Nij Smellinghe Hospital, Drachten, the Netherlands;2. VASCERN PPL European Reference Centre: French Reference Center Rare Vascular Diseases, Department of Lymphology, AP-HP, HEGP Hôpital Européen Georges Pompidou, Paris, France;4. SW Thames Centre for Genomics, St George''s University Hospitals NHS Foundation Trust, UK and St George''s University of London, London, UK;1. Çukurova University, Pediatric Metabolism and Nutrition Department, Adana, Turkey;2. Başakşehir Çam ve Sakura City Research and Education Hospital, Pediatric Metabolism Department, İstanbul, Turkey;3. University College London, Genetics and Genomics Medicine, Institute of Child Health London, UK;4. Çukurova University, Pediatric Intensive Care Department, Adana, Turkey;5. İnönü University, Pediatric Gastroenterology and Hepatology Department, Malatya, Turkey;6. Çukurova University, Medical Genetics Department, Adana, Turkey;7. Çukurova University, Pediatric Cardiology Department, Adana, Turkey;9. Sütçü İmam University, Pediatric Endocrinology Department, Kahramanmaraş, Turkey;1. Department of Medical Genetics, Christian Medical College and Hospital, Vellore, India;2. Department of Neurological Sciences, Christian Medical College and Hospital, Vellore, India;3. Department of Biochemistry, All India Institute of Medical Sciences, Kalyani, West Bengal, India;4. Department of Biochemistry and Medical Genetics, Xavier University School of Medicine, Aruba, The Kingdom of the Netherlands;5. Department of Clinical Genomics at Mayo Clinic, Jacksonville, FL, USA;1. Department of Pediatric Genetics, Samsun Education and Research Hospital, Samsun, Turkey;2. Deta-Gen Genetic Diseases Research Center, Kayseri, Turkey;3. Department of Medical Genetics, Samsun Education and Research Hospital, Samsun, Turkey;1. Medical Genetics Unit, Department of Clinical and Experimental Biomedical Sciences ‘Mario Serio’, University of Florence, Firenze, Italy;2. Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children''s Hospital, Firenze, Italy;3. Division of Neurosurgery - Meyer Children''s Hospital - University of Florence, Firenze, Italy;4. Pathology Unit, A. Meyer Children''s University Hospital, Firenze, Italy;5. Medical Genetics Unit, Meyer Children''s University Hospital, Firenze, Italy;6. Dpt. of Neuroscience, IRCCS Fondazione Stella Maris, Calambrone, Pisa, Italy;7. Dpt. of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;8. Medical Genetics Unit, Department of Medical Sciences and Public Health and CeSAR, University Service for Research, University of Cagliari, 09124, Cagliari, Italy;9. Medical Genetics Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy |
| |
| Abstract: | Hermansky-Pudlak syndrome (HPS) is a heterogeneous group of autosomal recessive genetic disorders characterized by oculocutaneous albinism, bleeding diathesis, and variable presentation of immune deficiency and dysregulation. The pathogenesis of HPS involves mutations in genes responsible for biogenesis and trafficking of lysosome-related organelles, essential for the function of melanosomes, platelet granules, and immune cell granules. Eleven genes coding for proteins in the BLOC-1, BLOC-2, BLOC-3 and AP-3 complexes have been implicated in the pathogenesis of HPS. To date, the rare subtype HPS-7 associated with bi-allelic mutations in DTNBP1 (dysbindin) has only been reported in 9 patients. We report a novel DTNBP1 splicing mutation in a 15-month-old patient with HPS-7 phenotype and severe inflammatory bowel disease (IBD). This patient's leukocytes have undetectable dysbindin protein. We also identify dysregulated expression of several genes involved in activation of the adaptive immune response. This case underscores the emerging immunological consequences of dysbindin deficiency and suggests that DTNBP1 mutations may underlie some rare cases of very early onset IBD. |
| |
| Keywords: | Hermansky-Pudlak syndrome HPS-7 Dysbindin Oculocutaneous albinism Very early onset IBD |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
