ANO5 mutations in the Dutch limb girdle muscular dystrophy population |
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| Authors: | Anneke J. van der Kooi Leroy ten Dam Wendy S. Frankhuizen Chiara S.M. Straathof Pieter A. van Doorn Marianne de Visser Ieke B. Ginjaar |
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| Affiliation: | 1. Department of Genetics, Counsyl, South San Francisco, California, USA;2. Department of Pathology, New York University, New York, New York, USA;3. Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA;4. Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA;5. Department of Computer Science, Stanford University, Stanford, California, USA;6. Department of Statistics, Stanford University, Stanford, California, USA.;1. Bioinformatics Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, (FG), Italy;2. Cardiovascular Department, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, (FG), Italy;3. Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, (FG), Italy;1. Myriad Women’s Health (formerly Counsyl), South San Francisco, CA, USA;2. Myriad Genetics, Salt Lake City, UT, USA;3. Guardant Health, Redwood City, CA, USA;4. Invitae, San Francisco, CA, USA;1. Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università di Napoli, Napoli, Italy;2. Telethon Institute of Genetics and Medicine, Pozzuoli, Italy;3. Dipartimento di Neuroscienze, Università degli Studi di Messina, Messina, Italy;4. IRCCS Fondazione Stella Maris, Pisa, Italy;5. IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy;6. A.O.R.N.A. Cardarelli, Napoli, Italy;7. Dipartimento di Neuroscienze, Istituto Besta, Milano, Italy;8. Center of Myology and Neurodegenerative Disorders, Istituto Giannina Gaslini, Genova, Italy |
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| Abstract: | A Dutch cohort of 105 limb girdle muscular dystrophy (LGMD) patients were subject to subsequent genetic investigations. In half the families a causative mutation was found. Recently mutations were identified in ANO5 causing LGMD2L and Miyoshi-like myopathy (MMD3), but could also be found in patients with hyperCKemia only. Therefore, we analysed the index cases of the remaining 31 as yet undiagnosed families from our previously described cohort of LGMD patients for the presence of ANO5 mutations. Detailed history and neurological examination were available for all patients. Serum creatine kinase (CK) activity, skeletal muscle computed tomography (CT) and cardiological investigations were performed. Mutations in ANO5 were found in 16% of the families: 11 index patients and two sibs, eight males and five females. The founder mutation c.191dupA was present in 8 out of 13 patients. Ten different pathogenic mutations were identified of which seven were novel: five missense and two splice site mutations. The age of these patients ranged from 26 to 69 years and the age of onset varied from 21 to 57 years. Symptoms at onset were related to proximal leg weakness. The weakness was slowly progressive. Calf hypertrophy was present in three patients. Males were more severely affected than females. Serum CK activity was highly elevated in the early stage of disease and moderately increased in later stages. Muscle biopsy showed predominantly dystrophic changes. One patient had hypertrophic cardiomyopathy, two others had intraventricular septum thickening. |
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| Keywords: | Limb girdle muscular dystrophy LGMD Anoctamin 5 Frequency |
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