title: Severe hypohidrotic ectodermal dysplasia in a girl caused by a de novo 9;X insertion that includes XIST and disrupts the EDA gene.
abstract: X-linked hypohidrotic ectodermal dysplasia (XLHED) is caused by mutations in the EDA gene. A girl with severe hypohidrotic ectodermal dysplasia and normal mental development had completely skewed X chromosome inactivation with only the paternal X active in peripheral blood cells. Routine chromosome analysis and sequencing of the EDA gene were normal. However, whole chromosome painting revealed a 9;X insertion. FISH analyses with BAC probes towards the EDA gene and the more distal region containing the XIST locus showed that an X chromosome fragment of at least 4 Mb containing XIST was inserted into 9p13 in conjunction with a de novo pericentric inversion of chromosome 9. The proximal breakpoint was within the EDA gene and the distal breakpoint was distal to the XIST locus. Both parents had normal chromosomes, and the mother had random X inactivation in peripheral blood cells. Because XIST was lacking on the X chromosome with the disrupted EDA gene, the normal X chromosome was inactivated resulting in severe XLHED.
authors.affiliation: Department of Medical Genetics, Rikshospitalet-Radiumhospitalet Medical Center, 0027 Oslo, Norway. k.h.orstavik@medisin.uio.no
authors.forename: Karen Helene
authors.initials: KH
authors.lastname: Ørstavik
authors.forename: Gun Peggy S
authors.initials: GP
authors.lastname: Knudsen
authors.forename: Hilde
authors.initials: H
authors.lastname: Nordgarden
authors.forename: Eli
authors.initials: E
authors.lastname: Ormerod
authors.forename: Petter
authors.initials: P
authors.lastname: Strømme
authors.forename: Lazarous P
authors.initials: LP
authors.lastname: Lazarou
authors.forename: Lyndon G
authors.initials: LG
authors.lastname: Rosser
authors.forename: Trine
authors.initials: T
authors.lastname: Prescott
authors.forename: Gunnar
authors.initials: G
authors.lastname: Houge
mesh_terms: D002675:Child, Preschool; D020223:Chromosome Painting; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D004476:Ectodermal Dysplasia / Q000175:diagnosis / Q000235:genetics*; D053331:Ectodysplasins / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006197:Hair / Q000002:abnormalities; D006801:Humans; D009154:Mutation; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D017384:Sequence Deletion; D014071:Tooth Abnormalities / Q000235:genetics / Q000473:pathology; D049951:X Chromosome Inactivation
chemical_list: C506018:EDA protein, human; D053331:Ectodysplasins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA