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Mutations in the gene encoding the ATP dependent chromatin-remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital-urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar hypoplasia and distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model. We describe specific alterations in the precise spatio-temporal sequence of fissure formation during perinatal cerebellar development responsible for these foliation anomalies. The altered cerebellar foliation pattern in Chd7 haploinsufficient mice show some similarities to those reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we propose that mutations or polymorphisms in these genes may modify the cerebellar phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome indicate that a careful analysis of cerebellar foliation may be warranted in patients with CHARGE syndrome, particularly in patients with cerebellar hypoplasia and developmental delay.

Original publication




Journal article


Am J Med Genet C Semin Med Genet

Publication Date





CHARGE syndrome, CHD7, cerebellum, fissures, foliation, mouse, Animals, Biopsy, CHARGE Syndrome, Cerebellum, DNA-Binding Proteins, Developmental Disabilities, Disease Models, Animal, Genetic Association Studies, Genotype, Haploinsufficiency, Immunohistochemistry, In Situ Hybridization, Fluorescence, Magnetic Resonance Imaging, Mice, Mice, Transgenic, Nervous System Malformations, Phenotype