1. Mosaicism due to postzygotic mutations in women with focal dermal hypoplasia
- Author
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J. Küsel, Julien Thevenon, Emmanuelle Bourrat, Steffen Hörer, Rudolf Happle, Lisa Heinz, Pierre Vabres, Svenja Alter, Alrun Hotz, Andreas Zimmer, Judith Fischer, Fakultät für Biologie = Faculty of Biology [Freiburg], Albert-Ludwigs-Universität Freiburg, Center for Human Genetics Freiburg, Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), FHU TRANSLAD (CHU de Dijon), University of Freiburg [Freiburg], Department of Dermatology, University Medical Center Freiburg, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, and FHU TRANSLAD
- Subjects
Adult ,Zygote ,DNA Mutational Analysis ,Dermatology ,Biology ,Postzygotic mutation ,medicine.disease_cause ,PORCN ,Young Adult ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Missense mutation ,Goltz syndrome ,Skin ,Genetics ,Mutation ,Mosaicism ,Mouth Mucosa ,Genetic disorder ,High-Throughput Nucleotide Sequencing ,Membrane Proteins ,cutaneous mosaicism ,Karyotype ,medicine.disease ,Focal dermal hypoplasia ,3. Good health ,focal dermal hypoplasia ,Female ,Klinefelter syndrome ,Acyltransferases ,[SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology - Abstract
International audience; Focal dermal hypoplasia (FDH, Goltz syndrome, MIM: #305600) constitutes a rare multisystem genetic disorder of the skin, skeleton, teeth and eyes with considerable variation in the clinical features. FDH is transmitted as an X-linked dominant trait and is caused by mutations in PORCN. In males, hemizygous PORCN mutations are lethal in utero. Around 300 cases have been reported in the literature to date. About 10% of them are males presenting either Klinefelter syndrome (karyotype 47, XXY) or mosaicism of a postzygotic mutation. Here we describe four cases of women with typical features of FDH, in whom a PORCN mutation was found in DNA from affected cutaneous tissue but not in DNA from peripheral blood. This study suggests that mosaicism caused by a postzygotic mutation occurs more often than assumed to date in female patients with FDH. A negative analysis performed on peripheral blood DNA does not exclude the diagnosis of FDH and it is thereby of practical importance to analyse DNA from the affected skin in order to identify low level mosaicism and thus to improve diagnostic precision. In total, we found two missense variants, one novel indel and one novel splice site variant. Individuals harbouring postzygotic mosaicism run a risk of transmitting the disorder to their daughters, because the maternal mosaic could also affect the gonads. This article is protected by copyright. All rights reserved.
- Published
- 2018