Clinical, histological and molecular analysis in patients with congenital muscular dystrophy and collagen vi deficiency

• Grant number: 14/19285-8
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2015
• End date: January 31, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Umbertina Conti Reed
• Grantee: Umbertina Conti Reed
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Edmar Zanoteli ; Leslie Domenici Kulikowski

Abstract

The Congenital Muscular Dystrophies (CMD) are a clinically and genetically heterogeneous group of myopathies characterized by muscle hypotonia, delayed motor development and early onset of progressive muscle weakness with dystrophic pattern on muscle biopsy. Almost half of the cases is caused by deficiency of laminin-± 2 (merosin). Other protein deficiencies described include: collagen VI, selenoprotein N1, several glycosyltransferases responsible for glycosylation of ±-dystroglycan and lamin A/C. The aim of this study was to characterize the clinical, histological and molecular aspects in patients with CMD related to deficiency of collagen VI. For the molecular study two methodologies will be used: (1) screening of the entire genome for bead arrays and (2) next-generation sequencing (NGS) for investigation of mutations in COL6A1, COL6A2 and COL6A3 genes, both techniques using Illumina platforms, in patients with clinical and histological diagnosis of CMD in which the immunohistochemical study excluded merosin, dystrophin, dysferlin and sarcoglycans deficiency. Additionally, histological analysis of muscle biopsies will be revised. The expression of collagen VI in fibroblast cultures from patients with identified mutations will be also studied. Obtaining a combined clinical, histological and genomic profile, the different clinical forms of DMC by collagen VI deficiency, provide a better understanding of the basis of disease, an unambiguous molecular diagnosis and certainly contribute directly to effective treatment planning for patients with this disease. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ZANOTELI, EDMAR; SOARES, PRISCILLA SOUZA; SERAFIM DA SILVA, ANDRE MACEDO; CAMELO, CLARA GONTIJO; SANTOS MONTEIRO FONSECA, ALULIN TACIO QUADROS; VELOSO ALBUQUERQUE, MARCO ANTINIO; MARTINS MORENO, CRISTIANE ARAUJO; ABATH NETO, OSORIO LOPES; NOVO FILHO, GIL MONTEIRO; KULIKOWSKI, LESLIE DOMENICI; et al. Clinical features of collagen VI-related dystrophies: A large Brazilian cohort. CLINICAL NEUROLOGY AND NEUROSURGERY, v. 192, MAY 2020. (14/19285-8)