Confirming the recessive inheritance of PERP-related erythrokeratoderma

Clin Genet. 2020 Apr;97(4):661-665. doi: 10.1111/cge.13699. Epub 2020 Jan 12.

Abstract

Erythrokeratoderma (EK) is heterogeneous clinical entity characterized by excessive scaling with resulting erythrokeratotic plaques. Several genes have been linked to EK and they encode a number of proteins that are important for the integrity of the keratinocyte layer of the epidermis. PERP is a transcription factor that is activated by both p53 and p63. However, its deficiency in a mouse model appears to only recapitulate p63-mediated role in skin development and organization. We report an extended multiplex consanguineous family in which an EK phenotype with a striking similarity to that observed in Perp-/- mice, is mapped to an autozygous region on chromosome 6 that spans PERP. Whole-exome sequencing revealed a novel variant in PERP that fully segregated with the phenotype. Functional analysis of patient- and control-derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP. A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that recessive inheritance is also possible. Our results, therefore, support the establishment of an autosomal recessive PERP-related EK phenotype in humans.

Keywords: PERP; erythrokeratoderma; keratoderma; transgrediens.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Child
  • Child, Preschool
  • Epidermis / metabolism
  • Epidermis / pathology
  • Exome Sequencing
  • Gene Expression Regulation / genetics
  • Genes, Recessive / genetics
  • Genes, Tumor Suppressor
  • Homozygote
  • Humans
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Membrane Proteins / genetics*
  • Mice
  • Young Adult

Substances

  • Membrane Proteins
  • PERP protein, human
  • Perp protein, mouse

Supplementary concepts

  • Erythroleukemia, Familial