Confirming the recessive inheritance of PERP-related erythrokeratoderma |
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Authors: | Nisha Patel Salim Alkeraye Eman Alobeid Tarfa Alshidi Rana Helaby Firdous Abdulwahab Hanan E. Shamseldin Fowzan S. Alkuraya |
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Affiliation: | 1. Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia;2. Dermatology Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia |
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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. |
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Keywords: | erythrokeratoderma keratoderma PERP transgrediens |
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