Recessive mosaicism in ABCA12 causes blaschkoid congenital ichthyosiform erythroderma

F. S. van Leersum*, M. M. B. Seyger, T. E. J. Theunissen, E. M. H. F. Bongers, P. M. Steijlen, M. van Geel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


We report the unique case of a 3-year-old girl who presented with linear erythematosquamous lesions following the lines of Blaschko, suggestive of genetic mosaicism in the skin. Single-candidate gene analyses were performed on DNA from blood, excluding Conradi-Hunermann-Happle syndrome, erythrokeratodermia variabilis and a mosaic presentation of pityriasis rubra pilaris. With whole-exome sequencing (WES) on DNA from the patient's blood, a heterozygous missense mutation in exon 25 of the ABCA12 gene was detected. By manually scrutinizing the WES data, another low-percentage pathogenic frameshift mutation was found in the adjacent exon 26 of the same gene. This frameshift mutation was confirmed with Sanger sequencing in DNA isolated from a lesional skin biopsy. A subsequent cloning experiment was performed to prove that the patient is compound heterozygous for both mutations in the affected skin, explaining the blaschkoid ichthyosiform erythrodermic phenotype. The patient's phenotype was elucidated by the combination of a germline mutation and an acquired postzygotic mutation in ABCA12, resulting in the diagnosis of a mosaic manifestation of autosomal recessive congenital ichthyosis. Postzygotic compound allelic loss in autosomal recessive disorders is extremely rare and will not appear as the typical phenotype of the known germline mutation-associated disease. This is the first report of a proven biallelic mosaic presentation of an autosomal recessive genodermatosis, and we propose the term 'recessive mosaicism' for this kind of manifestation.

Original languageEnglish
Pages (from-to)208-211
Number of pages4
JournalBritish Journal of Dermatology
Issue number1
Early online date28 Jul 2019
Publication statusPublished - Jan 2020


  • SKIN


Dive into the research topics of 'Recessive mosaicism in ABCA12 causes blaschkoid congenital ichthyosiform erythroderma'. Together they form a unique fingerprint.

Cite this