After several years of study, visits and exams in Spain, the first publications about our 1F Limb-girdle Muscular Dystrophy were from 2000, with the article “Autosomal dominant limb-girdle muscular dystrophy. A large kindred with evidence for anticipation” (J. Gámez; C. Navarro; A.L. Andreu; J.M. Fernandez; L. Palenzuela; S. Tejeira; R. Fernández–Hojas; S. Schwartz; C. Karadimas; S. DiMauro; M. Hirano; C. Cervera) where through 5 muscular biopsies and the study of 61 members of our family it was discovered that suffered from a unknown muscular dystrophy. From it, the authors of this study did a full genomic scan to identify the locus of the disease. In 2003 they published the study “A novel autosomal dominant limb-girdle muscular dystrophy (LGMD 1F) maps to7q32.1-32.2” (L.Palenzuela; A.L.Andreu ; J.Gámez; M.R.Vilà; T.Kumimatsu; A.Meseguer; C.Cervera; I.Fernández Cadenas; P.F.M. Van der Ven; T.G.Nygaard; E.Bonilla; and M. Hirano) with which it was discovered the locus of the disease and it was detected that there was no defect at the Filamin C or its protein product, genetical defect already known inside of this cromosomic region. With this study, it was clarified that we were in front of a new autosomic limb-girdle dominant dystrophy yet to be discovered and it was given to it the name of LGMD1F, following the classification adopted before for the other limb-girdle muscular diseases discovered, where the 1 number means that is dominant and the F that is the sixth variant discovered.
Until 2011 there were no other publications directly about LGMD1F and our family, when two Italian affected of LGMD1F, members of the same Spanish family, did a new biopsy and got published the results “LGMD 1(F) – A pathogenetic hypothesis based on histopathology and ultrastructure” (G. Cenacchi, E. Peterle, L. Tarantino, V. Papa, M. Fanin, C. Angelini) in where apart from being described the morphological and ultrastructural situation, there were also hypothesized other encoding proteins of the actin as possible responsibles of the LGMD1F pathogenic mechanism.
In 2012 it was published the study “Next generation sequencing applications are ready for genetic diagnosis of muscular dystrophies” (M. Savarese, A. Torella, M. Mutarelli, M. Dionisi, T. Giugliano, G. Di Fruscio, M. Iacomino, A. Garofalo, S. Aurino, F. Del Vecchio Blanco, G. Piluso, L. Politano, M. Fanin, C. Angelini 5, V. Nigro) where it was said that it had been identified the alteration of the Transportin 3 (TNPO3) in the LGMD1F affected patients.
It followed another study in 2012 entitled “Ultrastructural changes in LGMD1F” (G.Cenacchi, E. Peterle, M. Fanin, V.Papa, R. Salaroli, C. Angelini) where it got evidenced that the morphological and ultrastructural data suggested, in the LGMD1F studied cases, a phenotypic myopathy similar to those described by the Z-disk diseases, which leaded to the hypothesis that the mutant protein in LGMD1F can cause a decomposition of the cytoskeletal net related with desmin.
In 2013 there were published two more studies about the discovering of the genetical alteration which caused 1F Limb-girdle Muscular Dystrophy – LGMD1F.
One Spanish: “Limb-girdle muscular dystrophy 1F is caused by a microdeletion in the transportin
3 gene” (Maria J. Melià, Akatsuki Kubota, Saida Ortolano, Juan J. Vilchez, Josep Gámez,Kurenai Tanji, Eduardo Bonilla, Lluis Palenzuela, Israel Fernández-Cadenas, Anna Pristoupilová, Elena Garcia-Arumí, Antoni L. Andreu , Carmen Navarro,Michio Hirano, Ramón Martí) where it was proclaimed the identification of the 1F limb-girdle muscular dystrophy mutation’s cause, in a single nucleotide heterozygote deletion (c.2771del) at the termination codon of the Transportin 3 (TNPO3) and which was not known for being a key factor in the HIV importation to nucleus process.
And an Italian one: “Next-Generation Sequencing Identifies Transportin 3 as the Causative Gene for
LGMD1F” (Annalaura Torella, Marina Fanin, Margherita Mutarelli, Enrico Peterle, Francesca Del Vecchio Blanco, Rossella Rispoli, Marco Savarese, Arcomaria Garofalo, Giulio Piluso, Lucia Morandi, Giulia Ricci, Gabriele Siciliano, Corrado Angelini, Vincenzo Nigro), where it was explained the identification of a shared variance in the LGMD1F affected apart from the heterozygote mutation on TNPO3 gene and that the mutant TNPO3 was located around the nucleus, but not inside. The genetic implication connected with the transport to the nucleus suggests a new pathologic mechanism which leads to the muscular dystrophy.