ABSTRACT
Objective To analyze mutations in the GJB2 gene in a Chinese patient with keratitis-ichthyosis-deafness (KID)syndrome complicated by cutaneous squamous cell carcinoma. Methods Clinical data were collected from a patient with KID syndrome complicated by cutaneous squamous cell carcinoma. Peripheral blood samples were obtained from the patient and her parents, and DNA was extracted from these blood samples. PCR was performed to amplify the exon 2 of the GJB2 gene followed by direct DNA sequencing. Results A mutation (c.148G > A)was identified at position 148 in exon 2 of the GJB2 gene, which caused a codon change from GAC to AAC and resulted in the substitution of aspartate by asparagine at position 50 in the connexin26 (Cx26)protein (p.Asp50Asn). Inaddition,anothermutation(c. 79G > A), which led to the substitution of valine by isoleucine at codon 27 in Cx26 (p.Val27Ile), was found at position 79 in exon 2 of the GJB2 gene. Neither of the two mutations was detected in the patient′s parents. Literature review revealed that 13 cases of KID syndrome complicated by cutaneous squamous cell carcinoma had been reported in abroad, and the mutation c.148G > A was detected in the GJB2 gene in all the 7 cases finally diagnosed by gene sequencing. Conclusion GJB2 gene mutations may be responsible for the clinical phenotype of KID syndrome in this Chinese patient, and the mutation c.148G > A may be related to the development of cutaneous squamous cell carcinoma.
ABSTRACT
Asp66his, Asp54Lys, and Asp50Asn are mutations in connexin 26 that are observed in the clinic and give rise to autosomal dominant syndromes. They are the result of point mutations in the human gap junction beta-2 gene. In order to investigate the structural mechanism of Bart-Pumphrey Syndrome, Keratitis-Ichthyosis-Deafness Syndrome, and Vohwinkel Syndrome, homology modeling was carried out. Asp66 has direct contact with Asn62 by two hydrogen bonds in the wild-type protein, and in Asp66His, the biggest change observed is a tremendous energy increase caused by hydrogen bond breakage to Asn62. Shifts in the side chain and new hydrogen bond formation are observed for Lys54 compared to the wild-type protein (Asn54) and result in closer contact to Val84. Asp50Asn causes a significant decrease in bond energy, and residual charge reversal repels the ion and metabolites and, hence, inhibits their transportation. Such perturbations are likely to be a factor contributing to abnormal functioning of ion channels, resulting cell death and disease.