[Novel compound heterozygous mutations of TGM1 gene identified in a Chinese collodion baby].

OBJECTIVE

To identify potential mutations in a Chinese collodion baby.

METHODS

The patient was investigated clinically. DNA was extracted from peripheral blood of the baby and his parents. All coding exons(exons 2-15) and splicing sites of transglutaminase 1(TGM1) were amplified by polymerase chain reaction (PCR). Mutation detection was performed by directed sequencing of the PCR products. A total of 100 healthy unrelated subjects were used as controls. Haplotypes were constructed with microsatellites flanking the locus, and TGM1 genotypes of the family were used to determine parental origins of the mutations. CLUSTAL X (1.81) was employed to analyze cross-species conservation of the mutant protein sequence.

RESULTS

The boy was found to be a compound heterozygote for two novel mutations: c.420A>G (I140M) from his father and c.832G>A (G278R) from his mother, with the former occurring in the transglutaminase N domain and the latter between transglutaminase N and transglutaminase-like domains. Both mutations were absent from the control subjects.

CONCLUSION

The boy's condition was caused by two novel compound heterozygous mutations of c.420A>G and c.832G>A of TGM1. Author's results may provide new clues for molecular diagnosis of this disease.