The 10 autosomal recessive limb-girdle muscular dystrophies.
Fifteen forms of limb-girdle muscular dystrophies (5 autosomal dominant and 10 autosomal recessive) have already been found. The 10 genes responsible for the autosomal recessive forms, which account for more than 90% of the cases, had their product identified. This review will focus on the most recent data on autosomal recessive-limb-girdle muscular dystrophy and on our own experience of more than 300 patients studied from 120 families who were classified (based on DNA, linkage and muscle protein analysis) in eight different forms of autosomal recessive-limb-girdle muscular dystrophy. Genotype-phenotype correlations in this highly heterogeneous group confirm that patients with mutations in different genes may be clinically indistinguishable. On the other hand, for most forms of autosomal recessive-limb-girdle muscular dystrophy a discordant phenotype, ranging from a relatively severe course to mildly affected or asymptomatic carriers may be seen in patients carrying the same mutation even within the same family. A gender difference in the severity of the phenotype might exist for some forms of autosomal recessive-limb-girdle muscular dystrophy, such as calpainopathy and telethoninopathy but not for others, such as dysferlinopathies or sarcoglycanopathies. Understanding similarities in patients affected by mutations in different genes, differences in patients carrying the same mutations or why some muscles are affected while others are spared remains a major challenge. It will depend on future knowledge of gene expression, gene and protein interactions and on identifying modifying genes and other factors underlying clinical variability.
Zatz
Mayana
M
Human Genome Research Center, Departamento de Biologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matão 277, Cidade Universitária, CEP 05508-900, Sao Paulo, Brazil. mayazatz@usp.br
de Paula
Flavia
F
Starling
Alessandra
A
Vainzof
Mariz
M
D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D000073939:Dysferlin; D005808:Genes, Recessive; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008565:Membrane Proteins; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009136:Muscular Dystrophies / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010641:Phenotype
D003598:Cytoskeletal Proteins; C114839:DYSF protein, human; D000073939:Dysferlin; D005819:Genetic Markers; D008565:Membrane Proteins; D009124:Muscle Proteins