Pathogenic mutations in GLI2 cause a specific phenotype that is distinct from holoprosencephaly

Mutations in GLI2 have been associated with holoprosencephaly (HPE), a neuroanatomic anomaly resulting from incomplete cleavage of the developing forebrain, and an HPE-like phenotype involving pituitary anomalies and polydactyly. We collected the largest sample to date of individuals with variants affecting GLI2 and characterized their phenotype. This included previously published cases as well as new unpublished individuals. We found that individuals with mutations resulting in loss of function rather (versus those with variants of unknown significance) typically had a narrow phenotype including polydactyly and pituitary anomalies as well as subtle facial features, as opposed to frank HPE. (By Kelly Bear, http://jmg.bmj.com/content/early/2014/04/17/jmedgenet-2013-102249 )