Periventricular heterotopia: new insights into Ehlers-Danlos syndrome.
Nature often employs similar mechanisms to complete similar tasks, thus the evolution of homologous proteins across various organ systems to perform similar but slightly different functions. In this respect, disorders attributed to specific genetic mutations, while initially thought to be restricted in function and purpose, may provide broad insight into general cellular and molecular mechanisms of development and maintenance. One such example can be seen in the brain malformation, periventricular heterotopia (PH), which is characterized by very specific nodules of neurons that line the lateral ventricles beneath the cerebral cortex. PH is seen as a disorder of neuronal migration and can be caused by mutations in filamin A (FLNA), which encodes an actin-binding protein that regulates the cytoskeleton and cell motility. Recent advances in our understanding of the genetic causes of PH suggest that mutations in this gene, however, are also associated with the connective tissue disorder, Ehlers-Danlos syndrome (EDS), in which affected individuals present with joint and skin hyperextensibility and vascular problems including aortic dissection, excessive bleeding and bruisability. While much still remains unknown regarding the mechanistic role of FLNA in giving rise to PH and EDS, a common cellular and molecular basis likely gives rise to these two seemingly unrelated clinical disorders.
Sheen
Volney L
VL
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
Walsh
Christopher A
CA
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000473:pathology; D001921:Brain / Q000002:abnormalities*; D001927:Brain Diseases / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D002490:Central Nervous System / Q000473:pathology; D041321:Chromosomes, Human, X / Q000648:ultrastructure; D003094:Collagen / Q000737:chemistry; D003285:Contractile Proteins / Q000737:chemistry / Q000235:genetics; D004535:Ehlers-Danlos Syndrome / Q000175:diagnosis* / Q000473:pathology*; D064448:Filamins; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D012306:Risk
D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins; D003094:Collagen