ABSTRACT
Background@#Epidermolysis bullosa (EB) is a rare genetic disease with widely different clinical manifestations, but the relationship between genotype and phenotype is not fully understood. In the present study, we recruited a Chinese family in which two members had been diagnosed with localized EB simplex (EBS), with clinical manifestation, including blisters and erosions on the soles of the feet since infancy. @*Objective@#To identify and confirm the genetic variation in a Chinese family diagnosed as localized EBS. @*Methods@#Our study included two patients, other healthy members of the family, and 100 normal controls. Genomic DNA samples were isolated from each participant, and then polymerase chain reaction (PCR) direct sequencing was performed. @*Results@#The results of PCR direct sequencing revealed a novel heterozygous missense mutation in codon 461 of exon 7 of KRT5 (c.1382T＞C), which led to an amino acid change (p.L461P) in the patients with EBS but was absent in unaffected family members and 100 unrelated control samples. @*Conclusion@#The present study broadens the mutational spectrum of EBS, and this knowledge could be harnessed for prenatal screening, gene diagnosis, and gene therapy for lo-calized EBS.
ABSTRACT
<p><b>OBJECTIVE</b>To analyze the clinical characteristics and causative mutation in an ethnic Han Chinese family affected with punctate palmoplantar keratoderma (PPPK).</p><p><b>METHODS</b>Clinical characteristics and inheritance pattern of the family were analyzed. Two seriously affected individuals from the family were investigated by whole exome sequencing. Three healthy individuals from the family and 120 non-PPPK individuals were evaluated to validate the result.</p><p><b>RESULTS</b>The family was characterized by keratotic papules on the palms and soles, which gradually increased in size and number with age and coalesced with each other, particularly over the pressure part of the palms and soles. The family has featured autosomal dominant inheritance. A heterozygous frameshift variant c.419delC in exons of the CELA1 gene was identified in all affected individuals but not among non-affected members.</p><p><b>CONCLUSION</b>A heterozygous frameshift variant c.419delC in CELA1 gene probably underlies the disease in the family affected with PPPK.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Base Sequence , Frameshift Mutation , Heterozygote , Keratoderma, Palmoplantar , Genetics , Molecular Sequence Data , Mutation , Pancreatic Elastase , Genetics , PedigreeABSTRACT
AIM:To investigate the expression of C/EBP homologous protein (CHOP) and its correlation with proliferative/apoptotic ratio (PAR) in colorectal adenoma-carcinoma sequence under the same genetic background .ME-THODS:Four kinds of tissue samples under the same genetic background from 23 patients, including normal colorectal tissue, adenoma with low-grade intraepithelial neoplasia , adenoma with high-grade intraepithelial neoplasia and colorectal adenocarcinoma samples , were collected .TUNEL method and Ki-67 immunohistochemistry were applied to determine the PAR.The expression of CHOP was detected by immunohistochemistry SABC method .RESULTS: ( 1 ) Under the same genetic background , the level of CHOP expression is significantly higher in colorectal adenocarcinoma than that in the ade -noma with high-grade intraepithelial neoplasia , the adenoma with low-grade intraepithelial neoplasia and the normal muco-sa.The level of CHOP expression was significantly higher in the adenoma with high -grade intraepithelial neoplasia than that in the adenoma with low-grade intraepithelial neoplasia and the normal mucosa .The level of CHOP expression was signifi-cantly higher in the adenoma with low-grade intraepithelial neoplasia than that in normal mucosa .(2) Under the same ge-netic background , PAR was significantly higher in the colorectal adenocarcinoma than that in the adenoma with high -grade intraepithelial neoplasia , the adenoma with low-grade intraepithelial neoplasia and the normal mucosa .PAR was significant-ly higher in the adenoma with high-grade intraepithelial neoplasia than that in the adenoma with low-grade intraepithelial neoplasia and the normal mucosa .PAR was significantly higher in the adenoma with low-grade intraepithelial neoplasia than that in the normal mucosa.(3) CHOP levels were positively correlated with PAR in the adenoma with low-grade intraepi-thelial neoplasia , adenoma with high-grade intraepithelial neoplasia and colorectal adenocarcinoma .CONCLUSION:CHOP expression and PAR continuously increased and positively correlated along the adenoma -carcinoma sequence , indica-ting that endoplasmic reticulum stress mediates the carcinogenesis of colorectal adenomas .