title: Dysregulation of FOXG1 by ring chromosome 14.
abstract: In this study we performed molecular characterization of a patient with an extra ring chromosome derived from chromosome 14, with severe intellectual disability, epilepsy, cerebral paresis, tetraplegia, osteoporosis and severe thoraco-lumbal scoliosis. Array CGH analysis did not show any genomic imbalance but conventional karyotyping and FISH analysis revealed the presence of an interstitial 14q12q24.3 deletion and an extra ring chromosome derived from the deleted material. The deletion and ring chromosome breakpoints were identified at base-pair level by mate-pair and Sanger sequencing. Both breakpoints disrupted putative long non-coding RNA genes (TCONS00022561;RP11-148E17.1) of unknown function. However, the proximal breakpoint was 225 kb downstream of the forkhead box G1 gene (FOXG1), within the known regulatory landscape of FOXG1. The patient represents the first case of a r(14) arising from an interstitial excision where the phenotype is compatible with dysregulation of FOXG1. In turn, the phenotypic overlap between the present case, the FOXG1 syndrome and the r(14) syndrome supports that dysregulation of FOXG1 may contribute to the classical r(14)-syndrome, likely mediated by dynamic mosaicism.
authors.affiliation: Department of Cellular and Molecular Medicine, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Daniela
authors.initials: D
authors.lastname: Alosi
authors.affiliation: Department of Cellular and Molecular Medicine, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark ; Danish Epilepsy Centre, Dianalund, Denmark.
authors.forename: Laura Line
authors.initials: LL
authors.lastname: Klitten
authors.affiliation: Department of Cellular and Molecular Medicine, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Bak
authors.affiliation: Danish Epilepsy Centre, Dianalund, Denmark ; Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Helle
authors.initials: H
authors.lastname: Hjalgrim
authors.affiliation: Danish Epilepsy Centre, Dianalund, Denmark ; Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Rikke Steensbjerre
authors.initials: RS
authors.lastname: Møller
authors.affiliation: Department of Cellular and Molecular Medicine, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Tommerup
keywords: 14q12; Dynamic mosaicism; Epilepsy; FOXG1; Intellectual disability; Ring chromosome 14