Akademik Veri Yönetim Sistemi
NEUROLOGY-GENETICS, cilt.7, sa.3, 2021 (SCI-Expanded)
Dominant negative or haploinsufficient mutations in the collagen genes COL4A1 and COL4A2 are characterized by arterial basement membrane thickening resulting in a multisystem microangiopathy targeting the CNS but also potentially affecting the ocular, renal, cardiac, and muscular systems. Within the brain, such changes predispose affected individuals to recurrent ischemic and/or hemorrhagic strokes beginning during early fetal development but extending into the postnatal period and even into adulthood.(1) Mutations affecting glycine residues of the Gly-Xaa-Yaw (typically representing glycine-proline-4-trans-hydroxyproline in vertebrates) repeat domains that typify collagens usually manifest in an autosomal dominant (AD) fashion. However, recent work suggests that tissue-specific mutation effects may also occur, with mutations leading to gain of function effects in some tissues and loss of function effects in others.(2) Stroke-related complications may be insidious and clinically silent. Neuroimaging phenotypes of COL4A-associated disease include chronic white matter disease, porencephaly/hydranencephaly, encephalomalacia, cerebral calcifications, schizencephaly and hydrocephalus and corresponding clinical diagnoses of cerebral palsy, intellectual disability, cortical visual impairment, and epilepsy.(3)