Publication Date:
2016-04-21
Description:
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 foetuses with PPSN, one with large pink exophytic tumours, the other with minor features but close microscopic findings. We performed whole exome sequencing in affected skin tissue from foetus 1 which identified a postzygotic de novo FGFR2 c.1144T〉C (p.Cys382Arg) mutation in 34.6 % of reads which was absent in blood from his parents. Targeted deep sequencing of FGFR2 confirmed its mosaic status in additional affected skin from foetus 1, and identified the same substitution in 26% of reads in affected skin from foetus 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 nevi (KEN). 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. This article is protected by copyright. All rights reserved.
Print ISSN:
0007-0963
Electronic ISSN:
1365-2133
Topics:
Medicine
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