Abstract: Autosomal recessive congenital ichthyosis (ARCI) is a non-syndromic congenital disorder of cornification characterized by abnormal scaling of the skin. The three major phenotypes are lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis. ARCI is caused by biallelic mutations in ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, NIPAL4, PNPLA1, SDR9C7, SULT2B1, and TGM1. The most severe form of ARCI, harlequin ichthyosis, is caused by mutations in ABCA12. Mutations in this gene can also lead to congenital ichthyosiform erythroderma or lamellar ichthyosis. We present a large cohort of 64 patients affected with ARCI carrying biallelic mutations in ABCA12. Our study comprises 34 novel mutations in ABCA12, expanding the mutational spectrum of ABCA12-associated ARCI up to 217 mutations. Within these we found the possible mutational hotspots c.4541G>A, p.(Arg1514His) and c.4139A>G, p.(Asn1380Ser). A correlation of the phenotype with the effect of the genetic mutation on protein function is demonstrated. Loss-of-function mutations on both alleles generally result in harlequin ichthyosis, whereas biallelic missense mutations mainly lead to CIE or LI

Abstract: Genodermatoses are monogenetic disorders, which may manifest with symptoms either exclusively on the skin or also involve other organs in the context of an associated syndrome. Over the past 30 years, numerous hereditary hair, tumor, blistering, and keratinization diseases have been characterized both clinically and genetically. This has resulted in the continuous development of disease-specific classifications as well as diagnostic algorithms and examination techniques, and has also led to new pathogenesis-based therapeutic approaches. While the deciphering of the underlying genetic defects of these diseases is already well advanced, there is still much room for the development of new translationally motivated treatment strategies

Abstract: Genodermatosen sind monogen vererbte Erkrankungen, die sich entweder ausschließlich mit Symptomen an der Haut manifestieren oder im Rahmen eines assoziierten Syndroms auch andere Organe betreffen können. In den zurückliegenden 30 Jahren wurden zahlreiche hereditäre Haar-, Tumor-, blasenbildende und Keratinisierungskrankheiten klinisch und genetisch charakterisiert. Dies hat zur kontinuierlichen Weiterentwicklung krankheitsspezifischer Klassifikationen sowie diagnostischer Algorithmen und Untersuchungstechniken geführt, aber auch zu neuen Pathogenese-basierten Therapiekonzepten. Während die Entschlüsselung der diesen Krankheiten zugrundeliegenden Gendefekte bereits weit fortgeschritten ist, gibt es noch viel Raum für die Entwicklung neuer translationaler Behandlungsstrategien