Genotype-phenotype correlations in laminopathies: how does fate translate?
A-type laminopathies are a group of diseases resulting from mutations in the intermediate filament proteins lamin A and C (both encoded by the LMNA gene), but for which the pathogenic mechanisms are little understood. In some laminopathies, there is a good correlation between the presence of a specific LMNA mutation and the disease diagnosed. In others however, many different mutations can give rise to the same clinical condition, even though the mutations may be distributed throughout one, or more, of the three functionally distinct protein domains of lamin A/C. Conversely, certain mutations can cause multiple laminopathies, with related patients carrying an identical mutation even having separate diseases, often affecting different tissues. Therefore clarifying genotype-phenotype links may provide important insights into both disease penetrance and mechanism. In the present paper, we review recent developments in genotype-phenotype correlations in laminopathies and discuss the factors that could influence pathology.
Scharner
Juergen
J
King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
Gnocchi
Viola F
VF
Ellis
Juliet A
JA
Zammit
Peter S
PS
D000818:Animals; D004195:Disease Models, Animal; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005838:Genotype; D006801:Humans; D034904:Lamin Type A / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009685:Nuclear Envelope / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation; D013577:Syndrome
D034904:Lamin Type A