I Vieitez1, P Gallano2, L González-Quereda2, S Borrego3, I Marcos3, J M Millán4, T Jairo4, C Prior5, J Molano5, M J Trujillo-Tiebas6, J Gallego-Merlo6, M García-Barcina7, M Fenollar8, C Navarro9. 1. Grupo de Patología Neonatal y Pediátrica, Enfermedades raras, Instituto de Investigación Biomédica de Ourense-Pontevedra-Vigo (IBI), Vigo, España; Complexo Hospitalario Universitario de Vigo (CHUVI), SERGAS, Vigo, España. 2. Departamento de Genética, Hospital de la Santa Creu i Sant Pau, Barcelona, España; CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, España. 3. Departamento de Genética, Reproducción y Medicina fetal, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, España; CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, España. 4. Unidad de Genética y Diagnóstico Prenatal, Hospital Universitario La Fe, Valencia, España; CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, España. 5. Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz, Madrid, España. 6. Departamento de Genética, Hospital Universitario Fundación Jiménez Díaz, Madrid, España; CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, España. 7. Unidad de Genética, Hospital Universitario de Basurto, Vizcaya, España. 8. Sección de Genética Clínica, Servicio de Análisis Clínicos, Hospital Clínico San Carlos, Madrid, España. 9. Complexo Hospitalario Universitario de Vigo (CHUVI), SERGAS, Vigo, España. Electronic address: cnavfer@sergas.es.
Abstract
INTRODUCTION: Duchenne muscular dystrophy (DMD) is a severe X-linked recessive neuromuscular disease that affects one in 3500 live-born males. The total absence of dystrophin observed in DMD patients is generally caused by mutations that disrupt the reading frame of the DMD gene, and about 80% of cases harbour deletions or duplications of one or more exons. METHODS: We reviewed 284 cases of males with a genetic diagnosis of DMD between 2007 and 2014. These patients were selected from 8 Spanish reference hospitals representing most areas of Spain. Multiplex PCR, MLPA, and sequencing were performed to identify mutations. RESULTS: Most of these DMD patients present large deletions (46.1%) or large duplications (19.7%) in the dystrophin gene. The remaining 34.2% correspond to point mutations, and half of these correspond to nonsense mutations. In this study we identified 23 new mutations in DMD: 7 large deletions and 16 point mutations. CONCLUSIONS: The algorithm for genetic diagnosis applied by the participating centres is the most appropriate for genotyping patients with DMD. The genetic specificity of different therapies currently being developed emphasises the importance of identifying the mutation appearing in each patient; 38.7% of the cases in this series are eligible to participate in current clinical trials.
INTRODUCTION:Duchenne muscular dystrophy (DMD) is a severe X-linked recessive neuromuscular disease that affects one in 3500 live-born males. The total absence of dystrophin observed in DMDpatients is generally caused by mutations that disrupt the reading frame of the DMD gene, and about 80% of cases harbour deletions or duplications of one or more exons. METHODS: We reviewed 284 cases of males with a genetic diagnosis of DMD between 2007 and 2014. These patients were selected from 8 Spanish reference hospitals representing most areas of Spain. Multiplex PCR, MLPA, and sequencing were performed to identify mutations. RESULTS: Most of these DMDpatients present large deletions (46.1%) or large duplications (19.7%) in the dystrophin gene. The remaining 34.2% correspond to point mutations, and half of these correspond to nonsense mutations. In this study we identified 23 new mutations in DMD: 7 large deletions and 16 point mutations. CONCLUSIONS: The algorithm for genetic diagnosis applied by the participating centres is the most appropriate for genotyping patients with DMD. The genetic specificity of different therapies currently being developed emphasises the importance of identifying the mutation appearing in each patient; 38.7% of the cases in this series are eligible to participate in current clinical trials.
Authors: Marianela Schiava; Rachel Amos; Henriette VanRuiten; Michael P McDermott; Williams B Martens; Stephanie Gregory; Anna Mayhew; Elaine McColl; Rabi Tawil; Tracey Willis; Kate Bushby; Robert C Griggs; Michela Guglieri Journal: Neurology Date: 2021-12-02 Impact factor: 9.910
Authors: Yi-Li Min; Hui Li; Cristina Rodriguez-Caycedo; Alex A Mireault; Jian Huang; John M Shelton; John R McAnally; Leonela Amoasii; Pradeep P A Mammen; Rhonda Bassel-Duby; Eric N Olson Journal: Sci Adv Date: 2019-03-06 Impact factor: 14.136
Authors: Nasser A Elhawary; Essam H Jiffri; Samira Jambi; Ahmad H Mufti; Anas Dannoun; Hassan Kordi; Asim Khogeer; Osama H Jiffri; Abdelrahman N Elhawary; Mohammed T Tayeb Journal: Hum Genomics Date: 2018-04-10 Impact factor: 4.639
Authors: Ricardo Santin; Igor Araujo Vieira; Jean Costa Nunes; Maria Luiza Benevides; Fernanda Quadros; Ana Carolina Brusius-Facchin; Gabriel Macedo; Ana Paula Santin Bertoni Journal: Acta Myol Date: 2021-06-30