Severe hypohidrotic ectodermal dysplasia in a girl caused by a de novo 9;X insertion that includes XIST and disrupts the EDA gene.
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.
Ørstavik
Karen Helene
KH
Department of Medical Genetics, Rikshospitalet-Radiumhospitalet Medical Center, 0027 Oslo, Norway. k.h.orstavik@medisin.uio.no
Knudsen
Gun Peggy S
GP
Nordgarden
Hilde
H
Ormerod
Eli
E
Strømme
Petter
P
Lazarou
Lazarous P
LP
Rosser
Lyndon G
LG
Prescott
Trine
T
Houge
Gunnar
G
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
C506018:EDA protein, human; D053331:Ectodysplasins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA