Gene Diagnosis In A Family Of Hidrotic Ectodermal Dysplasia

Background Ectodermal dysplasias (EDs) are developmental disorders affecting tissues of ectodermal origin including hair, nail, teeth and sweat glands. To date, more than 200 distinct EDs have been described, about 30 EDs have been diagnosed at the molecular level by the identification of the causative genes, however, EDs that involve only hair and nails are uncommon. EDs can be pure, affecting only ectodermal tissues, or comprise part of a syndrome. However, due to their variable clinical presentation, the diagnosis of different type of EDs may at times be difficult as they display only a few signs of a syndrome rather than the full phenotype or share several features in common with each other.Objective To confirm the diagnosis as well as the pathogenic gene underlying a family of ectodermal dysplasia suffering from only hair and nail abnormalities.Methods Genomic DNA was extracted from whole blood by routine phenol-chloroform methods from 7 affected and 15 unaffected individuals in the family. The whole coding region of candidate genes K16,K17,K6a,K6b and GJB6 were amplified by polymerase chain reaction(PCR). The PCR products were purified with Shrimp Alkaline and Exonuclease and sequenced by ABI PRISM 3700 DNA analyzer.The RNA of the proband's skin tissue were extracted, then the pathogenic gene was further confirmed at the mRNA level by RT-PCR.Results Upon mutation analysis, no keratin gene mutation(K16,K17,K6a and K6b) was detected. A heterozygous missense mutation 31G→A in the GJB6 gene was detected in all patients, which leds to the substitution of glycine by arginine at codon 11 on the N-terminal of the protein(G11R), the point mutation was not found in 15 normal individuals in this family. The mutation was also confirmed in cDNA originating from the proband's skin biopsy.Conclusions In our study, all patients carry a missense mutation G11R in the GJB6 gene that have been shown preciously to cause hidrotic ectodermal dysplasia (HED). We confirmed the family with HED at the molecular level by the identification of the causative genes and our finding further support that GJB6 gene G11R mutation is major molecular bases of HED pathogenesis.