Coexistence of mutations in keratin 10 (KRT10) and the mitochondrial genome in a patient with ichthyosis with confetti and Leber's hereditary optic neuropathy

Abstract

Ichthyosis with confetti (IWC) is a severe congenital genodermatosis characterized by ichthyosiform erythroderma since birth and confetti-like spots of normal skin appearing in childhood as a results of revertant mosaicism. This disorder is caused by mutations in KRT10 or KRT1 genes. We report a 16-year-old boy who presented ichthyosiform erythroderma with severe desquamation since birth and gradually worsening psycho-neurological symptoms (mental retardation, ataxia, dystonia, hypoacusis). The patient conspicuously lacked typical confetti-like spots at the age of 16. The molecular diagnostics by the whole exome sequencing showed a novel de novo (c.1374-2A>C) mutation in the KRT10 gene responsible for the development of IWC (KRT10 defect was confirmed by immunofluorescent study). Concurrently, the m.14484T>C mutation in mitochondrial MTND6 gene (characteristic for Leber's hereditary optic neuropathy or LHON) was detected in patient, his mother and brother. LHON causes frequent inherited blindness typically appearing during young adult life whose expression can be triggered by additional factors such as smoking or alcohol exposure. We speculate the effects of KRT10 and LHON mutations influence each other-skin inflammatory reaction due to severe ichthyosis might trigger the development of psychoneurological abnormalities whereas the mitochondrial mutation may reduce revertant mosaicism phenomenon resulting in the lack of confetti-like spots characteristic for IWC. However, based on a single case we should be cautious about attributing phenotypes to digenic mechanisms without functional data.

Use of dual genomic sequencing to screen mitochondrial diseases in pediatrics: a retrospective analysis

“…However, the lack of functional data has confused the digenic mechanisms. The relationship between nDNA and mtDNA was determined by observing attributing phenotypes, such as KRT10 and MT-ND6 38 , MT-ND1/MT-ND4 and OPA1, MT-ND1/MT-ND4 and RTN4IP1, ND4 and TMEM126A 39 . A single case could not easily distinguish the contribution of two genes, particularly both causative genes of similar MDs, as in our patients.…”

TMT-labeling Proteomics of Papillary Thyroid Carcinoma Reveal Invasive Biomarkers

“…S1 ).29 genes were correlated with tumoirgenesis of thyroid cancer and 90 genes were specific to invasion. KRT10 was reported to be correlated with the stability of skin structure and is often mutated in ichthyosis with confetti, a skin disorder 23 . Downregulation of KRT10 indicates its pathological roles in invasion initiation and in PTC pathology.…”

Identification of the molecular cause of episodic progressive hearing loss in a patient with enlarged vestibular aqueduct and dysplasia of mid-peak section of the cochlea

“…Obraz taki mógł sugerować chorobę mitochondrialną, jako dodatkową komponentę wyjaśniającą część objawów. Podobne przypadki współistnienia dwóch niezależnych chorób uwarunkowanych genetycznie opisywano w literaturze [35]. W badaniach molekularnych wykluczono obecność wariantu m.3243A>G sprawczego dla zespołu MELAS, w toku analizy całej sekwencji DNA mitochondrialnego zidentyfikowano wariant m.961T>G zlokalizowany w genie MT-RNR1 kodującym mitochondrialne 12S rRNA.…”