title: A 2.0 Mb microdeletion in proximal chromosome 14q12, involving regulatory elements of FOXG1, with the coding region of FOXG1 being unaffected, results in severe developmental delay, microcephaly, and hypoplasia of the corpus callosum.
abstract: We identified 2.0 Mb of a novel deletion on chromosome 14q12, involving 8 genes and putative regulatory elements of FOXG1 by array CGH in a patient with severe growth and psychomotor retardation, hypotonia, microcephaly, dysmorphic face, and hypoplasia of the corpus callosum. Case of a submicroscopic 14q12 deletion, involving regulatory elements of FOXG1, with the coding region of FOXG1 being unaffected, is extremely rare. Using fibroblast cell line established from the patient, we showed that the expression level of FOXG1 in our patient was decreased. Our finding provides additional evidence that not only over-dosage of FOXG1 as previously mentioned, under-dosage of FOXG1 is also associated with phenotype, overlapping between congenital variant of Rett syndrome with FOXG1 mutations and 14q12 microdeletion, not including the coding region of FOXG1. Though the gene dosage of FOXG1 appears to be critical for the normal development of brain, the complex mechanism of its regulation of gene expression remains to be elucidated.
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan; Department of Endocrinology and Metabolism, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Takagi
authors.forename: Goro
authors.initials: G
authors.lastname: Sasaki
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Mitsui
authors.forename: Misa
authors.initials: M
authors.lastname: Honda
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hasegawa
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D061085:Agenesis of Corpus Callosum / Q000175:diagnosis / Q000235:genetics*; D002478:Cells, Cultured; D002648:Child; D002872:Chromosome Deletion; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D003337:Corpus Callosum / Q000473:pathology; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics; D050436:Regulatory Elements, Transcriptional / Q000235:genetics
chemical_list: C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins
keywords: 14q12; Array CGH assay; FOXG1; PRKD1; Regulatory elements