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Genotype-Phenotype Correlation in Trichilemmal Cysts

      Trichilemmal cysts (TCs) present both in autosomal dominant patterns and sporadic patterns (
      • Friedrich R.E.
      • Wilczak W.
      Multiple trichilemmal cysts of the scalp.
      ;
      • Seidenari S.
      • Pellacani G.
      • Nasti S.
      • Tomasi A.
      • Pastorino L.
      • Ghiorzo P.
      • et al.
      Hereditary trichilemmal cysts: a proposal for the assessment of diagnostic clinical criteria.
      ). Recently,
      • Hörer S.
      • Marrakchi S.
      • Radner F.P.W.
      • Zolles G.
      • Heinz L.
      • Eichmann T.O.
      • et al.
      A monoallelic two-hit mechanism in PLCD1 explains the genetic pathogenesis of hereditary trichilemmal cyst formation.
      and later ourselves (
      • Kolodney M.S.
      • Coman G.C.
      • Smolkin M.B.
      • Hagen R.
      • Katzman J.A.
      • Katzman S.N.
      • et al.
      Hereditary trichilemmal cysts are caused by two hits to the same copy of the phospholipase C Delta 1 Gene (PLCD1).
      ) independently demonstrated that the p.Ser460Leu PLCD1 variant (NM_006225.4:c.1379 G > A, rs75495843) was the most common risk allele for TCs. A somatic ser745leu PLCD1 mutation was also present in all familial TCs examined. Surprisingly, a ser745leu somatic mutation was always on the same chromosome as the germline p.Ser460Leu variant, in contradiction to the dogma of Knudson’s two hit hypothesis (
      • Knudson Jr., A.G.
      Mutation and cancer: statistical study of retinoblastoma.
      ). In our previous study, only one of 17 patients with familial TCs did not harbor a germline p.Ser460Leu variant. That patient had a rare germline p.Glu455Lys (NM_006225.4:c.1363 G > A, rs141555869) variant in PLCD1, suggesting that this variant was a candidate for a second risk allele.

      Abbreviations:

      MRI (magnetic resonance imaging), TC (trichilemmal cyst), WT (wild type)
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