Ketatin10 Mutation In A Pedigree With Bullous Congenital Ichthyosiform Erythroderma And Clinical Observation Of Retinoic Acid Treatment

IntroductionIcthyosis is a group of partners with dry skin has the characteristics of its adequate adhesiveness squames hyperkeratotic abnormal inherited disease.According to the genetic mechanism, clinical manifestation and histopathology, mainly divides into four type:ichthyosis vulgaris(IV),epidermolytic hyperkeratosis(EHK),X-linked ichthyosis(XLI),nonbullous congenital ichthyosiform erythroderma(NCIE).EHK is a rare autosomal dominant inherited disease,its incidence is 0.33/10 million-1/10 million.90% of the patients in 1 age have skin lesions,71% born with, about half patients have a positive family history.This disease has high spontaneous mutation rate, at least half of the cases are volatile.This study used directly sequencing method to detect all the genes of KRT10 and KRT1 in this family, especially hot zone coding genetic mutations in order to discover new disease mutations and further enrich the gene mutations spectrum.Materials and Methods1.Materials(1) Research object:A han epidermolytic hyperkeratosis family of liaoning diagnosied by depatment of dermatology of the first affiliated hospital of china medical university.Mother and son are patients,and they have the same clinical manifestations.(2) Major reagents:10%SDS,EDTA,boric acid,proteinase K,Tris saturated phenol,chloroform,alcohol,ethidium bromide,agarose,TBE buffer,2xTaq plus PCR Master Mix.2.MethodsPunch biopsies were taken from typical lesions for histopathological examination by light microscopy. Genomic DNA was extracted from the blood samples of the family and 50 normal human controls.Mutations of keratin1(KRT1) and keratin 10 (KRT10) were detected by polymerase chain reaction(PCR) and DNA sequencing.The propositus was given the third generation retinoic acid when was diagnosed,cooperate with the oral medication.ResultsThere was a single heterozygous point mutation in KRT10 gene, i.e.2140 G→A of KRT10,leading to an amino acid alteration of arginine to histidine (KRT10 R156H).Retinoic acid treatment after four months, symptoms improved obviously, skin squames thinner.ConclusionKRT10 R156H mutations were the cause of the phenotype in this two cases, and further confirmed that R156H in KRT10 is likely to be a mutation hotspot in people with EHK, then provide some experiment evidence for gene diagnosis and gene treatment.Retinoic acid treatment effect is remarkable.