Heterogeneous pathogenesis of LGMD 2 : consequences for therapy

Autosomal recessive limb girdle muscular dystrophies (LGMD type 2) are a clinically and genetically heterogeneous group of disorders, including at least 13 different genetic entities, which are characterized by progressive involvement and wasting of proximal limb girdle muscles. All LGMD2 seem to be present worldwide, though the relative frequency of the different types is variable. The gold standard for LGMD diagnosis is the study of protein involved either by immunoblot or immunohistochemistry on the basis of clinical phenotypes, followed by a mutation study in candidate genes. Pathogenetic mechanisms are various; a different pathophysiology implies different clinical muscle involvement and might require a differential therapeutical approach.

[1]  I. Richard,et al.  AAV-mediated delivery of a mutated myostatin propeptide ameliorates calpain 3 but not α-sarcoglycan deficiency , 2007, Gene Therapy.

[2]  I. Richard,et al.  Phenotypic correction of alpha-sarcoglycan deficiency by intra-arterial injection of a muscle-specific serotype 1 rAAV vector. , 2007, Molecular therapy : the journal of the American Society of Gene Therapy.

[3]  I. Richard,et al.  Ins and outs of therapy in limb girdle muscular dystrophies. , 2007, The international journal of biochemistry & cell biology.

[4]  M. Battaglia,et al.  Allogeneic mesoangioblasts give rise to alpha-sarcoglycan expressing fibers when transplanted into dystrophic mice. , 2006, Experimental cell research.

[5]  Susan C. Brown,et al.  Fukutin gene mutations in steroid‐responsive limb girdle muscular dystrophy , 2006, Annals of neurology.

[6]  J. Molkentin,et al.  Age-dependent effect of myostatin blockade on disease severity in a murine model of limb-girdle muscular dystrophy. , 2006, The American journal of pathology.

[7]  I. Richard,et al.  Safety and efficacy of AAV-mediated calpain 3 gene transfer in a mouse model of limb-girdle muscular dystrophy type 2A. , 2006, Molecular therapy : the journal of the American Society of Gene Therapy.

[8]  Irccs Bambino.  Expanding the clinical spectrum of POMT1 phenotype , 2006 .

[9]  E. Kudryashova,et al.  Trim32 is a ubiquitin ligase mutated in limb girdle muscular dystrophy type 2H that binds to skeletal muscle myosin and ubiquitinates actin. , 2005, Journal of molecular biology.

[10]  Yuko Kobayashi,et al.  Protective effects of Ca2+ handling drugs against abnormal Ca2+ homeostasis and cell damage in myopathic skeletal muscle cells. , 2005, Biochemical pharmacology.

[11]  C. Angelini,et al.  Extensive scanning of the calpain-3 gene broadens the spectrum of LGMD2A phenotypes , 2005, Journal of Medical Genetics.

[12]  E. Kudryashova,et al.  Calpain 3 participates in sarcomere remodeling by acting upstream of the ubiquitin-proteasome pathway. , 2005, Human molecular genetics.

[13]  D. Muruve,et al.  Immune responses to adeno-associated virus vectors. , 2005, Current gene therapy.

[14]  J. Emparanza,et al.  LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene. , 2005, Brain : a journal of neurology.

[15]  C. Angelini,et al.  The frequency of limb girdle muscular dystrophy 2A in northeastern Italy , 2005, Neuromuscular Disorders.

[16]  C. Angelini,et al.  Ultrastructural changes in dysferlinopathy support defective membrane repair mechanism , 2005, Journal of Clinical Pathology.

[17]  C. Esapa,et al.  Fukutin-related protein mutations that cause congenital muscular dystrophy result in ER-retention of the mutant protein in cultured cells. , 2005, Human molecular genetics.

[18]  O. Hummel,et al.  Dysferlin-Deficient Muscular Dystrophy Decay-Accelerating Factor / CD 55 in Attack due to Down-Regulation of Increased Susceptibility to Complement , 2005 .

[19]  C. Angelini,et al.  Molecular diagnosis in LGMD2A: Mutation analysis or protein testing? , 2004, Human mutation.

[20]  K. Bushby,et al.  Limb‐girdle muscular dystrophies – from genetics to molecular pathology , 2004, Neuropathology and applied neurobiology.

[21]  Chien-Chang Chen,et al.  Defective membrane repair in dysferlin-deficient muscular dystrophy , 2003, Nature.

[22]  C. Angelini,et al.  LGMD2E patients risk developing dilated cardiomyopathy , 2003, Neuromuscular Disorders.

[23]  I. Nishino,et al.  Localization of calpain 3 in human skeletal muscle and its alteration in limb-girdle muscular dystrophy 2A muscle. , 2003, Journal of biochemistry.

[24]  Susan C. Brown,et al.  Functional requirements for fukutin-related protein in the Golgi apparatus. , 2002, Human molecular genetics.

[25]  Giorgio Valle,et al.  Gene expression profiling in dysferlinopathies using a dedicated muscle microarray. , 2002, Human molecular genetics.

[26]  K. Patel,et al.  Titin‐cap associates with, and regulates secretion of, Myostatin , 2002, Journal of cellular physiology.

[27]  Leena Peltonen,et al.  Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin. , 2002, American journal of human genetics.

[28]  J. Beckmann,et al.  Stable expression of calpain 3 from a muscle transgene in vivo: Immature muscle in transgenic mice suggests a role for calpain 3 in muscle maturation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Susan C. Brown,et al.  Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C. , 2001, Human molecular genetics.

[30]  L. Peltonen,et al.  Secondary calpain3 deficiency in 2q-linked muscular dystrophy , 2001, Neurology.

[31]  K. Campbell,et al.  Early adenovirus-mediated gene transfer effectively prevents muscular dystrophy in alpha-sarcoglycan-deficient mice , 2000, Gene Therapy.

[32]  M. Hamida,et al.  A new locus for autosomal recessive limb-girdle muscular dystrophy in a large consanguineous Tunisian family maps to chromosome 19q13.3 , 2000, Neuromuscular Disorders.

[33]  I. Nonaka,et al.  Mutations of calpain 3 gene in patients with sporadic limb-girdle muscular dystrophy in Japan , 1999, Journal of the Neurological Sciences.

[34]  J. Sanes,et al.  ε-Sarcoglycan Replaces α-Sarcoglycan in Smooth Muscle to Form a Unique Dystrophin-Glycoprotein Complex* , 1999, The Journal of Biological Chemistry.

[35]  K. Bushby,et al.  Making sense of the limb-girdle muscular dystrophies. , 1999, Brain : a journal of neurology.

[36]  C. Angelini,et al.  The clinical spectrum of sarcoglycanopathies , 1999, Neurology.

[37]  J. Beckmann,et al.  Calpain 3 deficiency is associated with myonuclear apoptosis and profound perturbation of the IkBa/NF-kB pathway in limb-girdle muscular dystrophy type 2A , 1999, Nature Medicine.

[38]  Paul Young,et al.  Structural basis for activation of the titin kinase domain during myofibrillogenesis , 1998, Nature.

[39]  N. Forsberg,et al.  Role of calpain in skeletal-muscle protein degradation. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Pieter J. de Jong,et al.  Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy , 1998, Nature Genetics.

[41]  C. Angelini,et al.  Steroids in muscular dystrophy: where do we stand? , 1998, Neuromuscular Disorders.

[42]  E. Hoffman,et al.  Homozygous α‐sarcoglycan mutation in two siblings: One asymptomatic and one steroid‐responsive mild limb–girdle muscular dystrophy patient , 1998, Muscle & nerve.

[43]  J. Beckmann,et al.  Calpain-3 deficiency causes a mild muscular dystrophy in childhood. , 1997, Neuropediatrics.

[44]  M. Passos-Bueno,et al.  The seventh form of autosomal recessive limb-girdle muscular dystrophy is mapped to 17q11-12. , 1997, American journal of human genetics.

[45]  K. Bushby,et al.  The phenotype of chromosome 2p-linked limb-girdle muscular dystrophy , 1996, Neuromuscular Disorders.

[46]  D. Balcerzak,et al.  Evidence for implication of muscle-specific calpain (p94) in myofibrillar integrity. , 1996, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[47]  H. Sorimachi,et al.  Muscle-specific Calpain, p94, Responsible for Limb Girdle Muscular Dystrophy Type 2A, Associates with Connectin through IS2, a p94-specific Sequence (*) , 1995, The Journal of Biological Chemistry.

[48]  Isabelle Richard,et al.  Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A , 1995, Cell.

[49]  H. Kawasaki,et al.  Molecular cloning of a novel mammalian calcium-dependent protease distinct from both m- and mu-types. Specific expression of the mRNA in skeletal muscle. , 1989, The Journal of biological chemistry.

[50]  F. J. Nattrass,et al.  On the classification, natural history and treatment of the myopathies. , 1954, Brain : a journal of neurology.