Holoprosencephaly: a paradigm for the complex genetics of brain development.
Holoprosencephaly (HPE) is the most common major developmental defect of the forebrain in humans. Clinical expression is variable, ranging from a small brain with a single cerebral ventricle and cyclopia to clinically unaffected carriers in familial HPE. Significant aetiological heterogeneity exists in HPE and includes both genetic and environmental causes. Recently, defects in the cell signalling pathway involving the Sonic Hedgehog (SHH) gene, as well as defects in the cholesterol biosynthesis, have been shown to cause HPE in humans. These discoveries and current genetic approaches serve as a paradigm for studying normal and abnormal brain morphogenesis.
Roessler
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E
Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-1852, USA.
Muenke
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M
D000818:Animals; D001921:Brain / Q000002:abnormalities*; D016142:Holoprosencephaly / Q000235:genetics*; D006801:Humans; D009154:Mutation