Inherited ichthyoses: molecular causes of the disease in Czech patients

Abstract

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.

Genomic basis for skin phenotype and cold adaptation in the extinct Steller’s sea cow

“…1B) and are present in all our 12 sequenced individuals (section SM3), as well as in an additional individual recovered from the same site ( 14 ). In humans, inactivating variants with functional relevance in both genes have been described downstream of those present in Steller’s sea cow ( 15 – 17 ) (Fig. 1C) and are absent in healthy controls supporting the proposed functional relevance of the Steller’s sea cow’s pseudogenizations.…”

Molecular analysis of inherited disorders of cornification in Polish patients show novel variants and functional data and provokes questions on the significance of secondary findings.

“…The overrepresentation of ALOX12B patients was also noticed among Czech ARCI patients, where 18/47 (38%) probands had ALOX12B pathogenic variants [14]. This is in contrast to Austrian patients, where the TGM1 gene was mostly causative (9/30 ARCI genotyped patients, 28%) [12].…”

Randbetonte erythematöse Plaques bei einem Patienten mit kongenitaler Ichthyose: von häufigen und seltenen Dermatosen

“…21 % aller Fälle ausmachten, sind c.1889C>T (p.(Pro630Leu) und c.700C>T (p.Arg234*) [12,13]. Die bei unserem Patienten detektierte c.1392 + 2T>A-Variante, die vermutlich zu einem Speißeffekt führt, wurde bereits bei einem tschechischen Patienten [14,15] und von einer Tübinger Praxis für Humangenetik beschrieben [16].…”