Homozygous loss-of-function mutation in ALMS1 causes the lethal disorder mitogenic cardiomyopathy in two siblings |
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| Institution: | 1. Department of Emergency, Shanghai Pu Nan Hospital, Shanghai, China;2. Department of Neurosurgery, Shanghai Pu Nan Hospital, Shanghai, China;3. Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China;4. Department of Cardiovascular Research, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China;5. Department of Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China;1. Department of Pediatrics, Division of Pediatric Neurology and Metabolism, University Hospital Ghent, De Pintelaan 185, B-9000 Ghent, Belgium;2. Department of Pediatrics, Division of Pediatric Cardiology, University Hospital Ghent, De Pintelaan 185, B-9000 Ghent, Belgium;3. Laboratories of Neurogenetics and Ultrastructural Neuropathology and Biobank, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, B-2610 Antwerpen, Belgium;4. Neurogenetics Group, Department of Molecular Genetics, VIB, Universiteitsplein 1, B-2610 Antwerpen, Belgium;5. Research Group Reproduction and Genetics (REGE), Vrije Universiteit Brussel (VUB), Laarbeeklaan 101, B-1090 Brussels, Belgium;6. Center for Medical Genetics, UZ Brussel, Vrije Universiteit Brussel (VUB), Laarbeeklaan 101, B-1090 Brussels, Belgium;7. Department of Pathology, University Hospital Ghent, De Pintelaan 185, B-9000 Ghent, Belgium;8. Department of Neurology, University Hospital Antwerp, Wilrijkstraat 10, B-2650 Edegem, Belgium;1. National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Bethesda, MD, USA;2. The Jackson Laboratory, Bar Harbor, ME, USA;3. Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA;4. Section on Growth and Obesity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA;5. Departments of Pediatrics and Physiology, University of Tennessee Health Science Center, and Children''s Foundation Research Institute, Le Bonheur Children''s Hospital, Memphis, TN, USA;6. Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA;7. Johns Hopkins University School of Medicine, Department of Pediatrics and McKusick-Nathans Institute of Genetic Medicine, Baltimore, MD, USA |
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| Abstract: | BackgroundTwo siblings from consanguineous parents of Turkish descent presented with isolated dilated cardiomyopathy, leading to early death in infancy. The diagnosis of mitogenic cardiomyopathy was made histologically.Methods and resultsLinkage analysis combined with exome sequencing identified a homozygous deleterious mutation in the ALMS1 gene as the cause of this phenotype.ConclusionsAlström syndrome is characterized by a typically transient dilating cardiomyopathy in infancy, suggesting that mitogenic cardiomyopathy represents the extreme phenotype, resulting in demise before the other clinical symptoms become evident. This observation further illustrates the role of ALMS1 and cell cycle regulation. |
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| Keywords: | Cardiomyopathy Alström syndrome Exome sequencing Ciliopathy |
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