Queen Square Centre for Neuromuscular Diseases



Department of Neurosciences and Behavior Sciences, School of Medicine of Ribeirão Preto, University of São Paulo
Neurogenetics unit, University hospital, School of Medicine of Ribeirão Preto, University of São Paulo
Neuromuscular disorders section, University hospital, School of Medicine of Ribeirão Preto, University of São Paulo

University of Sao Paulo - Exterior

Lead PI: Wilson Marques Junior
Pedro José Tomaselli, Claudia Sobreira, Rosana H. Scola

University of Sao Paulo Team

Clinical neuromuscular expertise, patients and geographical region:
Our unit is the official referral centre for an area of five million inhabitants localized inside the State of São Paulo, but we receive patients from all over the country and other countries in South America.

We see about 120-150 patients per week, including ten new cases. These patients have neuropathy, myopathy, motor neuron disorders, hereditary spastic paraplegia and cerebellar ataxia.

Our team includes two Professors of Neurology, seven neuromuscular specialists; four first year and four second year neuromuscular residents, and a variable number of Masters and PhD students.

We do neurophysiology, nerve biopsy, muscle biopsy, muscle biochemistry and DNA tests.

Genetics and preclinical science expertise and facilities:
We are now able to genetically diagnose nine different neuropathies by Sanger or MLPA; twelve different ataxias; four motor neuron disorders; to sequence the mitochondrial DNA; and to test for nine different muscle diseases.

Additionally, we have four panels for neuropathies that test about 180 genes, and recently we approved a project to do 215 exomes. We are now receiving a panel for myopathies.

We are member and have scientific support from the Centre for Genomic Medicine that is led by a basic geneticist.

Our clinical laboratory is also testing antibodies for immune neuropathies.

Summary of current research programmes:
We are mostly interested in studying the genetic epidemiology and the genetic variability of our patients with neuropathy, myopathy, ataxia, HSP and motor neuron disorders, and establishing phenotype-genotype correlations, including neurophysiology and imaging.

We are also interested in the evaluation of environmental factors that may modify the clinical expression of the genetic diseases that we see.

Top five publications from the past five years:
SPG11 mutations cause widespread white matter and basal ganglia abnormalities, but restricted cortical damage. Faber I, Martinez ARM, de Rezende TJR, Martins CR Jr, Martins MP, Lourenço CM, Marques W Jr, Montecchiani C, Orlacchio A, Pedroso JL, Barsottini OGP, Lopes-Cendes Í, França MC Jr. Neuroimage Clin. 2018 Jun 9;19:848-857. doi: 10.1016/j.nicl.2018.05.031. eCollection 2018.

Intermediate-length CAG repeat in ATXN2 is associated with increased risk for amyotrophic lateral sclerosis in Brazilian patients. Tavares de Andrade HM, Cintra VP, de Albuquerque M, Piccinin CC, Bonadia LC, Duarte Couteiro RE, Sabino de Oliveira D, Claudino R, Magno Gonçalves MV, Dourado MET Jr, de Souza LC, Teixeira AL, de Godoy Rousseff Prado L, Tumas V, Bulle Oliveira AS, Nucci A, Lopes-Cendes I, Marques W Jr, França MC Jr

The genetic heterogeneity of hereditary transthyretin amyloidosis in a sample of the Brazilian population. Lavigne-Moreira C, Marques VD, Gonçalves MVM, de Oliveira MF, Tomaselli PJ, Nunez JC, do Nascimento OJM, Barreira AA, Marques W Jr. J Peripher Nerv Syst. 2018 Jun;23(2):134-137. doi: 10.1111/jns.12259. Epub 2018 Apr 10.

The frequency of the C9orf72 expansion in a Brazilian population. Cintra VP, Bonadia LC, Andrade HMT, de Albuquerque M, Eusébio MF, de Oliveira DS, Claudino R, Gonçalves MVM, Teixeira AL Jr, de Godoy Rousseff Prado L, de Souza LC, Dourado MET Jr, Oliveira ASB, Tumas V, França MC Jr, Marques W Jr. Neurobiol Aging. 2018 Jun;66:179.e1-179.e4. doi: 10.1016/j.neurobiolaging.2018.01.007. Epub 2018 Jan 31.

Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial. Schöls L, Rattay TW, Martus P, Meisner C, Baets J, Fischer I, Jägle C, Fraidakis MJ, Martinuzzi A, Saute JA, Scarlato M, Antenora A, Stendel C, Höflinger P, Lourenco CM, Abreu L, Smets K, Paucar M, Deconinck T, Bis DM, Wiethoff S, Bauer P, Arnoldi A, Marques W, Jardim LB, Hauser S, Criscuolo C, Filla A, Züchner S, Bassi MT, Klopstock T, De Jonghe P, Björkhem I, Schüle R. Brain. 2017 Dec 1;140(12):3112-3127. doi: 10.1093/brain/awx273.

How the new international centre will benefit our research and clinical programmes:
The international centre will offer an unique opportunity to improve the quality our expertise and access to the new techniques of Next Generation Sequencing. The access to these tests are very restricted in Brazil, and we will have an excellent opportunity to evaluate a large number of patients.

The opportunity to work with leading specialists in each of these areas will be the most important benefit. Actively participating in the process of seeing patients, investigating patients and then analysing the genetic basis of their disease will certainly permanently improve our quality as medical doctors and clinical scientists. This is an immeasurable acquisition that will be naturally transmitted to all our fellows.