Introduction:
The Brain Malformation Research Project
Research in our laboratory involves the field of developmental neurogenetics, especially the molecular characterization of human brain malformations. Specifically, we ascertain children and occasionally adults with brain malformations, obtain appropriate brain imaging studies and other clinical data, obtain DNA and other samples for our laboratory, identify and delineate new malformation syndromes, map and clone genes responsible for human malformation syndromes, and study the role of these genes in normal brain development and function.
Lissencephaly (smooth brain, agyria-pachygyria) is a severe brain malformation caused by incomplete neuronal migration to the cerebral cortex. We identified the first human lissencephaly gene, LIS1. Hemizygous deletion or mutation of this gene results in haploinsufficiency of the LIS1 protein and causes lissencephaly. A second gene causing lissencephaly has been identified on the X chromosome (XLIS or DCX), and mutations in this gene causes lissencephaly in hemizygous males and subcortical band heterotopia in carrier females.
While this program began with the study of lissencephaly (smooth brain), it has expanded to include several malformations of brain organogenesis and cortical development.
Examples of the former include
(1) holoprosencephaly,
(2) agenesis of the corpus callosum,
(3) Dandy-Walker malformations, and
(4) other hindbrain anomalies such as cerebellar hypoplasia and the brainstem-vermis decussation or "molar tooth" malformation. Malformations of cortical development consist of
(5) congenital or "primary" microcephaly;
(6) periventricular heterotopia,
(7) lissencephaly and subcortical band heterotopia, and
(8) polymicrogyria and schizen-cephaly.
For more information about the Lissencephaly Project and related research contact Mary King or click here.
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