MLPA followed by target-NGS to detect mutations in the dystrophin gene of Peruvian patients suspected of DMD/DMB

María Luisa Guevara-Fujita, Francia Huaman-Dianderas, Daisy Obispo, Rodrigo Sánchez, Victor Barrenechea, Diana Rojas-Málaga, Alejandro Estrada-Cuzcano, Milana Trubnykova, Mario Cornejo-Olivas, Victoria Marca, Bertha Gallardo, Milagros Dueñas-Roque, Ana Protzel, Carlos Castañeda, Hugo Abarca, Luis Celis, Jorge La Serna-Infantes, Ricardo Fujita

Research output: Contribution to journalArticlepeer-review

Abstract

Background: We report the molecular analysis of the DMD gene in a group of Peruvian patients with Duchenne/Becker dystrophinopathy. This is the first study to thoroughly characterize mutations in this population. Methods: We used the combination of multiplex ligation-dependent probe amplification (MLPA) and sequencing analysis of the DMD gene. We recruited Peruvian patients in 2 years from reference national hospitals. We performed DNA tests in 152 patients, checking first exon deletion/duplication by MLPA, and subsequently, if negative, samples were sequenced to detect point mutations. Results: The average age for diagnosis was 9.8 years, suggesting a delay for timely diagnosis and care. We found causal DMD mutations in 125 patients: 72 (57.6%) exon deletions/duplications (41.6% deletions, 16.0% duplications), and 53 (42.4%) point mutations (27.2% nonsense, 9.6% small indels, and 5.6% splice site). Conclusion: Due to our genetic background, we expected a higher number of novel and recurrent causal mutations in our sample. Results showed 16% of novel mutations, similar to other well-studied populations.

Original languageEnglish
Article numbere1759
JournalMolecular genetics & genomic medicine
Volume9
Issue number9
DOIs
StatePublished - Sep 2021

Bibliographical note

Funding Information:
The authors thank the participants and their relatives, the ADM-Peru, the physicians, including R. Yábar, J. Toro, A. Tori, R. Caparó, S. Samalvides, G. Chávez, and M. Chávez, and others who helped with sample collection and clinical exams. They also thank PTC Therapeutics and authorities at the Facultad de Medicina, Universidad de San Martín de Porres, who helped fund this study.

Publisher Copyright:
© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC

Keywords

  • Becker muscular dystrophy
  • Duchenne muscular dystrophy
  • molecular diagnosis
  • multiple ligation probe amplification
  • targeted Next Generation Sequencing

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