New splicing pathogenic variant in EBP causing extreme familial variability of Conradi-Hünermann-Happle Syndrome.

Autor: Pacault M; Service de génétique médicale, CHU Nantes, Nantes, France., Vincent M; Service de génétique médicale, CHU Nantes, Nantes, France. marie.vincent@chu-nantes.fr., Besnard T; Service de génétique médicale, CHU Nantes, Nantes, France., Kannengiesser C; Département de génétique, Hôpital Bichat, AP-HP, Paris, France., Bénéteau C; Service de génétique médicale, CHU Nantes, Nantes, France., Barbarot S; Service de dermatologie, CHU Nantes, Nantes, France., Latypova X; Service de génétique médicale, CHU Nantes, Nantes, France., Belabbas K; Laboratoire Commun de Biologie et Génétique Moléculaires (LCBGM), Hôpital Saint Antoine, AP-HP, Paris, France., Lamazière A; Plateforme de spectrométrie de masse (PM2), Hôpital Saint-Antoine, APHP, ERL Inserm U1157, UMR 7203, Paris, France., Winer N; Service de gynécologie-obstétrique, CHU Nantes, Nantes, France., Joubert M; Service d'anatomopathologie, CHU Nantes, Nantes, France., Bézieau S; Service de génétique médicale, CHU Nantes, Nantes, France., Isidor B; Service de génétique médicale, CHU Nantes, Nantes, France., Mercier S; Service de génétique médicale, CHU Nantes, Nantes, France., Nizon M; Service de génétique médicale, CHU Nantes, Nantes, France., Leclerc-Mercier S; Department of Dermatology, Reference Center for Genodermatoses (MAGEC), Necker-Enfants Malades Hospital (AP-HP), Imagine Institute, Paris Descartes-Sorbonne Paris-Cité University, Paris, France., Hadj-Rabia S; Department of Dermatology, Reference Center for Genodermatoses (MAGEC), Necker-Enfants Malades Hospital (AP-HP), Imagine Institute, Paris Descartes-Sorbonne Paris-Cité University, Paris, France., Dufernez F; Service de génétique, CHU de Poitiers, Poitiers, France.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2018 Dec; Vol. 26 (12), pp. 1784-1790. Date of Electronic Publication: 2018 Aug 22.
DOI: 10.1038/s41431-018-0217-0
Abstrakt: X-linked dominant chondrodysplasia punctata (CDPX2 or Conradi-Hünermann-Happle syndrome, MIM #302960) is caused by mutations in the EBP gene. Affected female patients present with Blaschkolinear ichthyosis, coarse hair or alopecia, short stature, and normal psychomotor development. The disease is usually lethal in boys. Nevertheless, few male patients have been reported; they carry a somatic mosaicism in EBP or present with Klinefelter syndrome. Here, we report CDPX2 patients belonging to a three-generation family, carrying the splice variant c.301 + 5 G > C in intron 2 of EBP. The grandfather carries the variant as mosaic state and presents with short stature and mild ichthyosis. The mother also presents with short stature and mild ichthyosis and the female fetus with severe limb and vertebrae abnormalities and no skin lesions, with random X inactivation in both. This further characterizes the phenotypical spectrum of CDPX2, as well as intrafamilial variability, and raises the question of differential EBP mRNA splicing between the different target tissues.
Databáze: MEDLINE
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