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Mosaic‐activating FGFR2 mutation in two fetuses with papillomatous pedunculated sebaceous naevus
Author(s) -
Kuentz P.,
Fraitag S.,
Gonzales M.,
Dhombres F.,
StOnge J.,
Duffourd Y.,
Joyé N.,
Jouannic J.M.,
Picard A.,
Marle N.,
Theve J.,
ThauvinRobinet C.,
Faivre L.,
Rivière J.B.,
Vabres P.
Publication year - 2017
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.14681
Subject(s) - mosaic , mutation , medicine , dermatology , biology , genetics , art , gene , visual arts
Summary 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 FGFR 2 c.1144T>C (p.Cys382Arg) mutation in 34·6% of reads which was absent in the parents’ blood. Targeted deep sequencing of FGFR 2 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. FGFR 2 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 FGFR 3 (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.