Gene Mapping and Mutation Identification in Patients with Primary Erythromelalgia / 中华皮肤科杂志

ABSTRACT

Objective To map the specific gene responsible for primary erythromelalgia and identify gene mutations in a Chinese family and one sporadic patient with primary erythromelalgia. Methods Geno-mic DNA was extracted from peripheral lymphocytes of the family members of the pedigree and the sporadic patient. Scanning the genes on chromosome 2q that had been identified was performed by using 6 microsatellite markers for the family members with primary erythromelalgia. Then linkage analysis and haplotype analysis were conducted. All exons of SCN9A gene were analyzed by PCR-DNA sequencing. The mutation identification was also confirmed by restriction fragment length polymorphism(RFLP). Results A maximum 2-point LOD score of 2.11 was found at a recombination fraction (? = 0.00) with markers D2S2370 and D2S2330. Recombination events were detected by markers D2S1353 and D2S2345 in this family by the haplotype analysis. There were two missense heterozygous point mutations in the 15th exon of SCN9A gene both in the family(T2573A) and the sporadic patient(T2543C), leading to the substitution of the amino acid leucine to histidine(L858H) and isoleucine to threonine(I848T), respectively. The above mutations were not found in 400 normal alleles. Conclusion It is proved that primary erythromelalgia is caused by mutations in SCN9A gene.