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Confirming the recessive inheritance of PERP ‐related erythrokeratoderma
Author(s) -
Patel Nisha,
Alkeraye Salim,
Alobeid Eman,
Alshidi Tarfa,
Helaby Rana,
Abdulwahab Firdous,
Shamseldin Hanan E.,
Alkuraya Fowzan S.
Publication year - 2020
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13699
Subject(s) - phenotype , biology , genetics , gene , exome sequencing
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.