Dear editor
Epidermolytic ichthyosis is a rare genetic disorder characterized by diffuse erythroderma from the time of birth with subsequent appearance of thick, brown scales and occasional blister formation. Mutation has been found in keratin 1 (K1) and keratin 10 (K10) genes.Citation1 Epidermolytic hyperkeratosis (EHK) is mostly inherited in a dominant mode. We report a Chinese family of EHK sufferers and their mutation findings.
The pedigree of the EHK family showed an autosomal dominant inheritance pattern (). The proband, a 41 year-old Chinese woman, had erythroderma on the head, trunk, and extremities. She exhibited skin blistering, erosions, erythrodermic, and hyperkeratosis on the skin since infancy and the blistering and erosion gradually diminished with age. Physical examination revealed hyperkeratosis of the entire body () and desquamation of the palm (). Her son, a 13 year-old boy, has a similar history and clinical manifestation. He was born with typical extensive erythroderma and bullae, and his skin was covered with hyperkeratotic patches of scales. Hyperkeratotic plaques can be seen on the back of the hand (), this lesion healed quickly after retinoid acid treatment (). Pathological examination of the upper portion of his left arm showed granular degeneration in the suprabasal layers ().
Direct sequencing of the whole coding regions of KRT1 and KRT10 was performed. A heterozygous KRT10 missense mutation c.467G>A(p.Arg156His) was identified in the proband and her son, while not in normal controls (). The mutation hotspots of EHK are located at the conserved sequences in helix initiative and helix terminal motifs of K1 and K10.Citation2 The mutation of the reported family, c.467G>A, just occurred at the hotspots. A previous study has revealed that the relationship between the genotype and phenotype in these patients was complex, not only dependent on the position of the mutation but also on the actual amino acid substitution.Citation3,Citation4 The p.R156 of KRT10 can be substituted by many amino acids such as serine, glycine, cysteine, histidine, and leucine, of which histidine is the most similar to arginine. Theoretically, the p.Arg156His mutation should be accompanied by a mild clinical manifestation,Citation3 but the reported patients experienced severe conditions. So we cannot conclude that the more similar between two amino acid substitution in the same codon, the milder consequence will be brought. The p.Arg156His mutation is rather common in previous reports,Citation2,Citation4 but the clinical manifestations vary greatly. Other genetic or epigenetic factors that were not identified may influence disease severity.
In conclusion, we confirm the diagnosis of epidermolytic ichthyosis in the two patients according to the genetic testing and this is beneficial for their genetic counseling. The results reveal that the mutation p.R156H of KRT10 is responsible for severe clinical manifestations in a Chinese family with EHK, and also confirm the complexity of the genotype–phenotype correlation in EHK.
Acknowledgments
We are indebted to the Foundation of PUMC innovation team, Teaching and Research Fund Project of PUMC (Grant No 2011zlgc0114, 303-05-8050).
Disclosure
No potential conflict of interest relevant to this work was reported.
References
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