Ørstavik Karen Helene, Knudsen Gun Peggy S, Nordgarden Hilde, Ormerod Eli, Strømme Petter, Lazarou Lazarous P, Rosser Lyndon G, Prescott Trine, Houge Gunnar
Department of Medical Genetics, Rikshospitalet-Radiumhospitalet Medical Center, 0027 Oslo, Norway.
Am J Med Genet A. 2007 Jul 1;143A(13):1510-3. doi: 10.1002/ajmg.a.31797.
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.
X连锁少汗型外胚层发育不良（XLHED）由EDA基因突变引起。一名患有严重少汗型外胚层发育不良且智力发育正常的女孩，其X染色体失活完全偏斜，外周血细胞中仅父源X染色体活跃。常规染色体分析及EDA基因测序均正常。然而，全染色体涂染显示存在9号与X染色体的插入。用针对EDA基因及包含XIST基因座的更远端区域的BAC探针进行的荧光原位杂交（FISH）分析表明，至少4 Mb包含XIST的X染色体片段与9号染色体的新发臂间倒位一起插入到9p13。近端断点位于EDA基因内，远端断点在XIST基因座的远端。父母双方染色体均正常，母亲外周血细胞中的X染色体随机失活。由于携带破坏EDA基因的X染色体上缺乏XIST，正常X染色体失活，导致严重的XLHED。
