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Br J Dermatol. 2017 Jan;176(1):204-208. doi: 10.1111/bjd.14681. Epub 2016 Oct 2.

Mosaic-activating FGFR2 mutation in two fetuses with papillomatous pedunculated sebaceous naevus.

Author information

1
Equipe d'Accueil 4271, Génétique des Anomalies du Développement, Université de Bourgogne Franche-Comté, F-21079, Dijon, France.
2
Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (TRANSLAD), Centre Hospitalo-Universitaire Dijon-Bourgogne, F-21079, Dijon, France.
3
Laboratoire de Génétique Chromosomique et Moléculaire, Plateau Technique de Biologie, Centre Hospitalo-Universitaire Dijon-Bourgogne, F-21079, Dijon, France.
4
Génétique Biologique Histologie, Centre Hospitalier Universitaire de Besançon, F-25000, Besançon, France.
5
Service d'Anatomie et de Cytologie Pathologiques, APHP, Groupe Hospitalier Necker-Enfants Malades, F-75743, Paris, France.
6
Service de Médecine Fœtale, Centre Pluridisciplinaire de Diagnostic Prénatal de l'Est Parisien, APHP, Hôpital Armand Trousseau, Université Pierre et Marie Curie, Paris, France.
7
Département de Génétique Médicale, APHP, Hôpital Armand Trousseau, Université Pierre et Marie Curie, Paris, France.
8
Service de Chirurgie Maxillo-Faciale et Chirurgie Plastique, APHP, Groupe Hospitalier Necker-Enfants Malades, F-75743, Paris, France.
9
Centre de Référence Malformations Rares de la Face et de la Cavité Buccale, UFR Paris Descartes Université, Paris, France.
10
Service de Pédiatrie 1 et de Génétique Médicale, Centre Hospitalo-Universitaire Dijon-Bourgogne, F-21079, Dijon, France.
11
Service de Dermatologie, Centre Hospitalo-Universitaire Dijon-Bourgogne, F-21079, Dijon, France.

Abstract

Papillomatous pedunculated sebaceous naevus (PPSN) has been described as a subtype of sebaceous naevus (SN), typically affecting the scalp and face. In contrast with Schimmelpenning syndrome, no cerebral, ocular or skeletal anomalies have hitherto been reported. We report two unrelated fetuses with PPSN, one with large pink exophytic tumours, the other with minor features but similar microscopic findings. We performed whole-exome sequencing in affected skin tissue from fetus 1, which identified a postzygotic de novo FGFR2 c.1144T>C (p.Cys382Arg) mutation in 34·6% of reads which was absent in the parents' blood. Targeted deep sequencing of FGFR2 confirmed its mosaic status in additional affected skin from fetus 1, and identified the same substitution in 26% of reads in affected skin from fetus 2. FGFR2 p.Cys382Arg is a known somatic driver mutation in human cancer, previously reported to result in activation of RAS signalling. A similar paralogous missense mutation in the transmembrane domain of FGFR3 (p.Gly380Arg) has been reported in keratinocytic epidermal naevi. Our findings define a distinct clinical and molecular subgroup of SN, beside HRAS or KRAS-related SN, and expand the spectrum of mosaic skin conditions associated with receptor tyrosine kinase mutations.

PMID:
27095246
DOI:
10.1111/bjd.14681
[Indexed for MEDLINE]

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