Clinical and genetic heterogeneity in laminopathies

作者：A. Bertrand, Khadija Chikhaoui, Rabah Ben Yaou, Gisèle Bonne · 发表于：Biochemical Society Transactions · 年份：2011 · DOI：10.1042/bst20110670 · 被引用次数：105 · 研究领域：Nuclear Structure and Function、RNA Research and Splicing、Skin and Cellular Biology Research

Mutations in the LMNA gene encoding lamins A/C are responsible for more than ten different disorders called laminopathies which affect various tissues in an isolated (striated muscle, adipose tissue or peripheral nerve) or systemic (premature aging syndromes) fashion. Overlapping phenotypes are also observed. Associated with this wide clinical variability, there is also a large genetic heterogeneity, with 408 different mutations being reported to date. Whereas a few hotspot mutations emerge for some types of laminopathies, relationships between genotypes and phenotypes remain poor for laminopathies affecting the striated muscles. In addition, there is important intrafamilial variability, explained only in a few cases by digenism, thus suggesting an additional contribution from modifier genes. In this regard, a chromosomal region linked to the variability in the age at onset of myopathic symptoms in striated muscle laminopathies has recently been identified. This locus is currently under investigation to identify modifier variants responsible for this variability.