title: Genetic profile of Brazilian patients with dystrophinopathies.
abstract: Different types of mutations in the DMD gene underlie Duchenne muscular dystrophies (DMD) and Becker muscular dystrophies (BMD). Large deletions and duplications are the most frequent causative genetic alterations worldwide, but little is known about DMD/BMD genetic profile in Brazil. Hence, we recruited patients with DMD and BMD from 8 neuromuscular reference centers along the country, and performed a comprehensive molecular investigation that included Multiplex Ligation-dependent Probe Amplification and Next generation sequencing (NGS) analyses. We evaluated 199 patients from 177 unrelated families: 166 with DMD, 32 with BMD and 1 1.5 years old asymptomatic patient with persistent hiperCKemia. Overall, large deletions (58.2%) followed by nonsense mutations (12.4%) and large duplications (11.3%) were the most frequent variants in Brazilian families. Large deletions were less frequent in BMD than in DMD (44.8% vs 60.8%). We identified 19 new DMD variants. Nonsense mutations were significantly more frequent in patients from northeastern region than from southern/southeastern regions of Brazil (27.7% vs 8.5%, P < .05). Genetic profile of Brazilian patients with DMD/BMD is similar to previously reported cohorts, but it is not uniform across the country. This information is important to plan rational clinical care for patients in face of the new coming mutation-specific therapies.
authors.affiliation: Department of Neurology, School of Medical Sciences, University of Campinas - UNICAMP, Campinas, Brazil.
authors.forename: P A D
authors.initials: PAD
authors.lastname: de Almeida
authors.affiliation: University Hospital Professor Edgard Santos, Federal University of Bahia (UFBA), Salvador, Brazil.
authors.forename: M C
authors.initials: MC
authors.lastname: Machado-Costa
authors.affiliation: University Hospital Professor Edgard Santos, Federal University of Bahia (UFBA), Salvador, Brazil.
authors.forename: G N
authors.initials: GN
authors.lastname: Manzoli
authors.affiliation: Department of Neurology, School of Medical Sciences, University of Campinas - UNICAMP, Campinas, Brazil.
authors.forename: L S
authors.initials: LS
authors.lastname: Ferreira
authors.affiliation: Specialized Health Care Unit for Children and Adolescents, University Hospital Cassiano Antonio Moraes, Federal University of Espírito Santo (UFES), Vitória, Brazil.
authors.forename: M C S
authors.initials: MCS
authors.lastname: Rodrigues
authors.affiliation: University Hospital Professor Edgard Santos, Federal University of Bahia (UFBA), Salvador, Brazil.|Hospital Infantil Nossa Senhora da Glória, Vitória, Brazil.
authors.forename: L S M
authors.initials: LSM
authors.lastname: Bueno
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
authors.forename: J A M
authors.initials: JAM
authors.lastname: Saute
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Pinto Vairo
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.|Molecular and Protein Analysis Unit, Hospital de Clínicas de Porto Alegre, Experimental Research Center, Porto Alegre, Brazil.
authors.forename: U S
authors.initials: US
authors.lastname: Matte
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.|Molecular and Protein Analysis Unit, Hospital de Clínicas de Porto Alegre, Experimental Research Center, Porto Alegre, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Siebert
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.|Molecular and Protein Analysis Unit, Hospital de Clínicas de Porto Alegre, Experimental Research Center, Porto Alegre, Brazil.
authors.forename: S L
authors.initials: SL
authors.lastname: Cossio
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
authors.forename: G S
authors.initials: GS
authors.lastname: Macedo
authors.affiliation: Neurology Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
authors.forename: P B
authors.initials: PB
authors.lastname: Winckler
authors.affiliation: Neuropediatrics Unit, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
authors.forename: M M
authors.initials: MM
authors.lastname: Becker
authors.affiliation: Federal University of Viçosa (UFV), Viçosa, Brazil.
authors.forename: L V B
authors.initials: LVB
authors.lastname: Magalhães
authors.affiliation: University of Joinville (UNIVILLE), Joinville, Brazil.
authors.forename: M V M
authors.initials: MVM
authors.lastname: Gonçalves
authors.affiliation: Clínica Marrone, Porto Alegre, Brazil.
authors.forename: C D
authors.initials: CD
authors.lastname: Marrone
authors.affiliation: Department of Neurology, School of Medical Sciences, University of Campinas - UNICAMP, Campinas, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Nucci
authors.affiliation: Department of Neurology, School of Medical Sciences, University of Campinas - UNICAMP, Campinas, Brazil.
authors.forename: M C
authors.initials: MC
authors.lastname: França
mesh_terms: D000293:Adolescent; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D016189:Dystrophin / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D020440:Gene Duplication / Q000235:genetics; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: C484258:DMD protein, human; D016189:Dystrophin
keywords: 
  DNA sequencing; 
  MLPA
  ; Becker muscular dystrophy; Duchenne muscular dystrophy; mutation