MYH9-related disease: Five novel mutations expanding the spectrum of causative mutations and confirming genotype/phenotype correlations |
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| Authors: | Daniela De Rocco Barbara Zieger Helen Platokouki Paula G Heller Annalisa Pastore Roberta Bottega Patrizia Noris Serena Barozzi Ana C Glembotsky Helen Pergantou Carlo L Balduini Anna Savoia Alessandro Pecci |
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| Institution: | 1. Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste, Italy;2. Department of Pediatric and Adolescent Medicine, University of Freiburg, Germany;3. Haemophilia Centre-Haemostasis Unit, “Aghia Sophia” Children''s Hospital, Athens, Greece;4. Department of Hematology Research, Instituto de Investigaciones Médicas Alfredo Lanari, University of Buenos Aires, CONICET, Argentina;5. National Institute for Medical Research, London, United Kingdom;6. Department of Internal Medicine, University of Pavia and IRCCS Policlinico San Matteo Foundation, Pavia, Italy;7. Department of Medical Sciences, University of Trieste, Trieste, Italy;1. Charles Nicolle Hospital, Congenital and Hereditary Diseases Tunis, Tunisia;2. University Tunis El Manar, Human Genetic Medical School Tunis, Tunisia;3. Pediatric Diseases, Regional Hospital of Bizerte Tunis, Tunisia;1. Wessex Clinical Genetics Service, University Hospital Southampton NHS Foundation Trust, Princess Anne Hospital, Coxford Road, Southampton, UK;2. Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, UK;3. Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury District Hospital, Salisbury, UK;4. Division of Human Genetics, University of Southampton, Southampton SO16 6YD, UK;1. Department of Pediatrics, University of Chicago, Chicago, IL, USA;2. Department of Neurology, University of Chicago, Chicago, IL, USA;3. Illinois College of Optometry, Chicago, IL, USA |
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| Abstract: | MYH9-related disease (MYH9-RD) is a rare autosomal dominant syndromic disorder caused by mutations in MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA (myosin-9). MYH9-RD is characterized by congenital macrothrombocytopenia and typical inclusion bodies in neutrophils associated with a variable risk of developing sensorineural deafness, presenile cataract, and/or progressive nephropathy. The spectrum of mutations responsible for MYH9-RD is limited. We report five families, each with a novel MYH9 mutation. Two mutations, p.Val34Gly and p.Arg702Ser, affect the motor domain of myosin-9, whereas the other three, p.Met847_Glu853dup, p.Lys1048_Glu1054del, and p.Asp1447Tyr, hit the coiled-coil tail domain of the protein. The motor domain mutations were associated with more severe clinical phenotypes than those in the tail domain. |
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