1. MYH9-Related Disease
- Author
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Roberto Ravazzolo, Marco Seri, Maria Savino, Alessandro Pecci, Filomena Di Bari, Patrizia Noris, Paolo Gresele, Anna Savoia, Pasi A. Koivisto, Simone Gangarossa, Carlo L. Balduini, Bianca Rocca, Carmine Pecoraro, Ilaria Longo, Juan Rodriguez Soriano, Gian Marco Ghiggeri, Roberto Cusano, Roberto Musso, Achille Iolascon, Nicola Bizzaro, Umberto Magrini, Alessandra Renieri, Emanuele Panza, Alessandra Nigro, Paola Malatesta, Seri, M, Pecci, A, DI BARI, F, Cusano, R, Savino, M, Panza, E, Nigro, A, Noris, P, Gangarossa, S, Rocca, B, Gresele, P, Bizzaro, N, Malatesta, P, Koivisto, Pa, Longo, I, Musso, R, Pecoraro, C, Iolascon, Achille, Magrini, U, RODRIGUEZ SORIANO, J, Renieri, A, Ghiggeri, Gm, Ravazzolo, R, Balduini, Cl, Savoia, A., Cusano, M, Bizzarro, N, Iolascon, A, Soriano, Jr, and Savoia, Anna
- Subjects
Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Pathology ,Adolescent ,Genotype ,Neutrophils ,Hearing loss ,Hearing Loss, Sensorineural ,DNA Mutational Analysis ,Cataract ,Diagnosis, Differential ,Variable Expression ,Cataracts ,medicine ,Humans ,Point Mutation ,Child ,Fechtner syndrome ,Aged ,Hematuria ,Purpura, Thrombocytopenic, Idiopathic ,Nephritis ,Myosin Heavy Chains ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Molecular Motor Proteins ,Nonmuscle Myosin Type IIA ,Sebastian Syndrome ,Syndrome ,General Medicine ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Pedigree ,Proteinuria ,Phenotype ,Epstein Syndrome ,May–Hegglin anomaly ,Female ,Sensorineural hearing loss ,medicine.symptom ,business - Abstract
May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are autosomal dominant macrothrombocytopenias distinguished by different combinations of clinical and laboratory signs, such as sensorineural hearing loss, cataract, nephritis, and polymorphonuclear Döhle-like bodies. Mutations in the MYH9 gene encoding for the nonmuscle myosin heavy chain IIA (NMMHC-IIA) have been identified in all these syndromes. To understand the role of the MYH9 mutations, we report the molecular defects in 12 new cases, which together with our previous works represent a cohort of 19 families. Since no genotype-phenotype correlation was established, we performed an accurate clinical and biochemical re-evaluation of patients. In addition to macrothrombocytopenia, an abnormal distribution of NMMHC-IIA within leukocytes was observed in all individuals, including those without Döhle-like bodies. Selective, high-tone hearing deficiency and cataract was diagnosed in 83% and 23%, respectively, of patients initially referred as having May-Hegglin anomaly or Sebastian syndrome. Kidney abnormalities, such as hematuria and proteinuria, affected not only patients referred as Fechtner syndrome and Epstein syndrome but also those referred as May-Hegglin anomaly and Sebastian syndrome. These findings allowed us to conclude that May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but rather a single disorder with a continuous clinical spectrum varying from mild macrothrombocytopenia with leukocyte inclusions to a severe form complicated by hearing loss, cataracts, and renal failure. For this new nosologic entity, we propose the term "MHY9-related disease," which better interprets the recent knowledge in this field and identifies all patients at risk of developing renal, hearing, or visual defects.
- Published
- 2003
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