MLPA followed by target‐NGS to detect mutations in the dystrophin gene of Peruvian patients suspected of DMD/DMB. Issue 9 (29th July 2021)

• Record Type: Journal Article
• Authors: Guevara‐Fujita, María Luisa; Huaman‐Dianderas, Francia; Obispo, Daisy; Sánchez, Rodrigo; Barrenechea, Victor; Rojas‐Málaga, Diana; Estrada‐Cuzcano, Alejandro; Trubnykova, Milana; Cornejo‐Olivas, Mario; Marca, Victoria; Gallardo, Bertha; Dueñas‐Roque, Milagros; Protzel, Ana; Castañeda, Carlos; Abarca, Hugo; Celis, Luis; La Serna‐Infantes, Jorge; Fujita, Ricardo
• Is Part Of: Molecular genetics & genomic medicine. Volume 9:Issue 9(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-29
• Subjects: Becker muscular dystrophy -- Duchenne muscular dystrophy -- molecular diagnosis -- multiple ligation probe amplification -- targeted Next Generation Sequencing; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.1759
• Languages: English
• ISSNs: 2324-9269

Abstract

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. Abstract : This study characterizes DMD/DMB mutations in Peru. This population has been poorly studied at the genetic level. We want to obtain a landscape of mutations affecting patients and give them treatment options with therapies currently under use in other countries. We found that deletions of the DMD gene, are predominant (41.6%) and point mutations with more than 40% of cases, explain the other cases. Duplications (16%) come in third place in this study. Regarding point mutations, the nonsense type (27%) is the most frequent change found.