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<p>The continuous renewal of healthy epidermis depends on the finely regulated proliferation of basal keratinocytes and subsequent differentiation as the newly formed cells move upwards through the epidermis. Perturbations in keratinocyte differentiation may lead to cornification disorders. We investigated seven dogs from four independent families that showed striking multifocal tree bark-like skin lesions. Histopathologically, lesional skin was characterized by pronounced epidermal hyperkeratosis. We therefore tentatively termed the phenotype phloiokeratosis, derived from the Greek word phloiós for tree bark. Whole genome sequencing revealed four independent variants in the <i>SUV39H1</i> gene encoding an H3K9 methyltransferase, which is involved in epigenetic silencing of chromatin. Phloiokeratosis is inherited as an X-chromosomal semi-dominant trait. Four of the affected dogs were heterozygous females and had lesion patterns reminiscent of Blaschko lines. In two of them, trio analyses experimentally confirmed <i>de novo</i> mutation events in the <i>SUV39H1</i> gene. Previously, <i>Suv39h1</i><sup><i>−/−</i></sup> knockout mice had been reported to have normal skin. So far, no human patients with <i>SUV39H1</i> loss-of-function variants have been reported. The findings in <i>SUV39H1</i> mutant dogs with phloiokeratosis for the first time link SUV39H1 deficiency to a heritable skin phenotype. Our study highlights the essential role of SUV39H1-mediated epigenetic silencing during normal keratinocyte differentiation.</p>

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Phloiokeratosis is a new ichthyosiform hyperkeratotic cornification disorder in dogs with SUV39H1 variants

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月25日

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  • Sarah Kiener,
  • Stefan J. Rietmann,
  • Sara Soto,
  • Sara J. Ramos,
  • Cherie M. Pucheu-Haston,
  • Chi-Yen Wu,
  • Desirae Wheatcraft,
  • Andrew Simpson,
  • Susanne Åhman,
  • Brett E. Wildermuth,
  • Michaela Drögemüller,
  • Vidhya Jagannathan,
  • Charles W. Bradley,
  • Elizabeth A. Mauldin,
  • Nadine M. Meertens,
  • Monika Welle,
  • Tosso Leeb

摘要

The continuous renewal of healthy epidermis depends on the finely regulated proliferation of basal keratinocytes and subsequent differentiation as the newly formed cells move upwards through the epidermis. Perturbations in keratinocyte differentiation may lead to cornification disorders. We investigated seven dogs from four independent families that showed striking multifocal tree bark-like skin lesions. Histopathologically, lesional skin was characterized by pronounced epidermal hyperkeratosis. We therefore tentatively termed the phenotype phloiokeratosis, derived from the Greek word phloiós for tree bark. Whole genome sequencing revealed four independent variants in the SUV39H1 gene encoding an H3K9 methyltransferase, which is involved in epigenetic silencing of chromatin. Phloiokeratosis is inherited as an X-chromosomal semi-dominant trait. Four of the affected dogs were heterozygous females and had lesion patterns reminiscent of Blaschko lines. In two of them, trio analyses experimentally confirmed de novo mutation events in the SUV39H1 gene. Previously, Suv39h1−/− knockout mice had been reported to have normal skin. So far, no human patients with SUV39H1 loss-of-function variants have been reported. The findings in SUV39H1 mutant dogs with phloiokeratosis for the first time link SUV39H1 deficiency to a heritable skin phenotype. Our study highlights the essential role of SUV39H1-mediated epigenetic silencing during normal keratinocyte differentiation.