Inherited ichthyoses belong to a large and heterogeneous group of mendelian disorders of cornification, and can be distinguished by the quality and distribution of scaling and hyperkeratosis, by other dermatologic and extracutaneous involvement, and by inheritance. We present the genetic analysis results of probands with X-linked ichthyosis, autosomal recessive congenital ichthyosis, keratinopathic ichthyosis, and a patient with Netherton syndrome. Genetic diagnostics was complemented by in silico missense variant analysis based on 3D protein structures and commonly used prediction programs to compare the yields of these two approaches to each other. This analysis revealed various structural defects in proteins coded by mutated genes while no defects were associated with known polymorphisms. Two patients with pathogenic variants in the ABCA12 gene have a premature termination codon mutation on one allele and a silent variant on the second. The silent variants c.69G > A and c.4977G > A are localised in the last nucleotide of exon 1 and exon 32, respectively, and probably affect mRNA splicing. The phenotype of both patients is very severe, including a picture harlequin foetus after birth; later (at 3 and 6 years of age, respectively) ectropin, eclabion, generalised large polygonal scaling and erythema.

1st Department of Pathological Anatomy Faculty of Medicine Masaryk University and St Anne's University Hospital Pekařská 664 53 656 91 Brno Czech Republic

Central European Institute of Technology Masaryk University Kamenice 753 5 625 00 Brno Czech Republic

Centre of Molecular Biology and Gene Therapy University Hospital Brno and Masaryk University Jihlavská 20 625 00 Brno Czech Republic

Department of Medical Genetics University Hospital Brno Jihlavská 20 625 00 Brno Czech Republic

Department of Pediatric Dermatology Pediatric Clinic University Hospital Brno and Masaryk University Jihlavská 20 625 00 Brno Czech Republic

Department of Public Health Faculty of Medicine Masaryk University Kamenice 5 625 00 Brno Czech Republic

GENNET Kostelní 9 292 170 00 Prague Czech Republic

Institute of Biology and Medical Genetics University Hospital Motol 5 Úvalu 84 150 06 Prague Czech Republic

Laboratory of Functional Genomics and Proteomics NCBR Faculty of Science Kotlářská 267 2 611 37 Brno Czech Republic

See more in PubMed

Oji V, Tadini G, Akiyama M, Blanchet Bardon C, Bodemer C, Bourrat E, et al. Revised nomenclature and classification of inherited ichthyoses: results of the first ichthyosis consensus conference in Soreze 2009. J Am Acad Dermatol. 2010;63:607–641. doi: 10.1016/j.jaad.2009.11.020. PubMed DOI

Buckova H, Noskova H, Borska R, Reblova K, Pinkova B, Zapletalova E, et al. Autosomal recessive congenital ichthyoses in the Czech Republic. Br J Dermatol. 2016;174:405–407. doi: 10.1111/bjd.13918. PubMed DOI

Akiyama M. ABCA12 mutations and autosomal recessive congenital ichthyosis: a review of genotype/phenotype correlations and of pathogenetic concepts. Hum Mutat. 2010;31:1090–1096. doi: 10.1002/humu.21326. PubMed DOI

Reblova K, Hruba Z, Prochazkova D, Pazdirkova R, Pouchla S, Zeman J, et al. Hyperphenylalaninemia in the Czech Republic: genotype-phenotype correlations and in silico analysis of novel missense mutations. Clin Chim Acta. 2013;419:1–10. doi: 10.1016/j.cca.2013.01.006. PubMed DOI

Skalova D, Zidkova J, Vohanka S, Mazanec R, Musova Z, Vondracek P, et al. CLCN1 mutations in Czech patients with myotonia congenita, in silico analysis of novel and known mutations in the human dimeric skeletal muscle chloride channel. PLoS One. 2013;8:e82549. doi: 10.1371/journal.pone.0082549. PubMed DOI PMC

Reblova K, Kulhanek P, Fajkusova L. Computational study of missense mutations in phenylalanine hydroxylase. J Mol Model. 2015;21:70. doi: 10.1007/s00894-015-2620-6. PubMed DOI

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–424. doi: 10.1038/gim.2015.30. PubMed DOI PMC