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Congenital aural atresia is a relevant diagnostic clue and a major recognizable feature of 18q deletion syndrome. Early diagnosis of 18q deletion syndrome may enable application of hearing aids. Knockout studies on the congenital aural atresia mouse gene homolog may add further insight into the genes responsible for this condition.

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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. Electronic supplementary material The online version of this article (10.1186/s13023-019-1076-7) contains supplementary material, which is available to authorized users.

DEAR EDITOR, Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin disorders characterized by blister formation. Classification of patients with EB begins with their separation into one of the four major EB groups, based on the level to which blisters develop: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB) and Kindler syndrome. The next level of subclassification takes into account the clinical features present in a given patient, most notably the distribution and severity of cutaneous and extracutaneous disease involvement. 1,2We started DNA analysis of EB in 2005 when polymerase chain reaction (PCR) direct sequencing of COL7A1, KRT5 and KRT14 was introduced in connection with clinical, ultrastructural and immunohistochemical analysis. 3,4 In 2014, we implemented PCR direct sequencing of TGM5 and the solution-based capture method SeqCap EZ Choice Library (Roche NimbleGen; Roche, Basel, Switzerland) and targeted resequencing. A custom capture array was designed to capture exons and adjacent intron sequences of 83 genes associated with genodermatoses, of which 18 genes are associated with an EB phenotype [TGM5, PKP1, DSP, JUP (suprabasal EBS); KRT5, KRT14, PLEC, EXPH5, DST (basal EBS); COL17A1, LAMA3, LAMB3, LAMC2, ITGA6, ITGB4, ITGA3 (JEB); COL7A1 (DEB); and FERMT1 (Kindler syndrome)].