Palmoplantar keratodermas

Gene: PERP

Amber List (moderate evidence)

PERP (PERP, TP53 apoptosis effector)
EnsemblGeneIds (GRCh38): ENSG00000112378
EnsemblGeneIds (GRCh37): ENSG00000112378
OMIM: 609301, Gene2Phenotype
PERP is in 2 panels

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on classification of this gene: The rating for this gene should be added as GREEN, as this gene has been implicated in Palmoplantar keratodermas, as identified from both monoallelic and biallelic variants from at least nine different families from multiple ethnicities, and supported by results from mouse models.

Heterozygous variants in PERP gene has been identified in five families (p.Tyr153* (c.459C>G, c.459C>A) and p.Trp151* (c.452G>A, c.453G>A)). These cause Olmsted syndrome-2 (OLMS-2, MIM# 619208), which is characterised by mutilating hyperkeratotic skin lesions, primarily on the palms and soles, but also extending onto dorsal surfaces of the hands and feet and distal extremities. However, two unrelated patients of Chinese ancestry identified with heterozygous mutation c.459C>A (p.Tyr153*) had more severe clinical manifestations such as more generalized lesions, alopecia universalis, intolerable itching, congenital hypotrichosis, and growth retardation.

Homozygous variants in PERP gene has been identified in four different families. p.Ser38Leufs*52 and p.Gly156Arg (c.466G>A) variants cause Erythrokeratodermia variabilis et progressiva-7 (EKVP7, MIM# 619209), which is characterised by palmoplantar keratoderma that extends to the dorsal surface of the hands and feet (transgrediens) and erythematous annular skin lesions. p.Leu30Pro (c.89T > C) and p.Gly156Arg (c.466G > C) variants cause ichthyosis (MONDO:0019269), palmoplantar keratoderma and dystrophic toe nails.

The association of PERP to OMS2 and EKVP7 has also been documented in OMIM, however the association to ichthyosis from a recent study from two unrelated multiplex consanguineous Iranian families has not yet been documented in OMIM.

The gene-disease association phenotypes from homozygous EKVP7 patients were supported by similar observations from Perp-/- mice. In addition, the functional analysis of patient- and control-derived keratinocytes revealed a deleterious effect on intracellular localisation of PERP.
Created: 9 Dec 2022, 5:56 p.m. | Last Modified: 9 Dec 2022, 5:56 p.m.
Panel Version: 2.1

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Olmsted syndrome-2, MIM# 619208, MONDO:003091; Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO:0030941; Ichthyosis, MONDO:0019269; Alopecia universalis; Congenital hypotrichosis

Publications

Rebecca Foulger (Genomics England curator)

Red List (low evidence)

This gene was part of an initial gene list collated by Thomas Cullup, GOSH and Veronica Kinsler, UCL, 25.Jan.2019 on behalf of the GMS Skin Specialist Test Group. Gene Symbol submitted: PERP; Suggested initial gene rating: Red; Evidence for inclusion: PMID:30321533; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided.
Created: 28 Jan 2019, 10:47 a.m.

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • London North GLH
  • NHS GMS
Phenotypes
  • Olmsted syndrome-2, MIM# 619208, MONDO:003091
  • Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO:0030941
  • Ichthyosis, MONDO:0019269
Tags
Q4_22_promote_green
OMIM
609301
Clinvar variants
Variants in PERP
Penetrance
None
Publications
Panels with this gene

History Filter Activity

9 Dec 2022, Gel status: 2

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q4_22_promote_green tag was added to gene: PERP.

9 Dec 2022, Gel status: 2

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: PERP were changed from Dominant and Recessive Keratoderma to Olmsted syndrome-2, MIM# 619208, MONDO:003091; Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO:0030941; Ichthyosis, MONDO:0019269

9 Dec 2022, Gel status: 2

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: PERP were set to 30321533

9 Dec 2022, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: perp has been classified as Amber List (Moderate Evidence).

18 Feb 2019, Gel status: 1

Added New Source

Rebecca Foulger (Genomics England curator)

Source London North GLH was added to PERP.

28 Jan 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Rebecca Foulger (Genomics England curator)

gene: PERP was added gene: PERP was added to Palmoplantar keratodermas. Sources: Expert Review Red,NHS GMS Mode of inheritance for gene: PERP was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: PERP were set to 30321533 Phenotypes for gene: PERP were set to Dominant and Recessive Keratoderma