Gene Mutation Analysis Of KLF7, CPO, LOC389071, CREB1 In A Pedigree With Hereditary Leukonychia Totalis

Background Leukonychia, known as white discoloration of the nails, was classified morphologically into four main types.totalis, partialis, striata, and punctuate. This disease can be caused by heredity, infection, intoxation and so on. Congenital leukonychia totalis is a rare nail disorder which may be hereditary. The reported Pedigrees were autosomal dominant inheritance forms. Presently preliminary progress with molecular genetics of leukonychia has been made by our .By genome scan on this family, we mapped the region on chromosome 2(2q32.3～2q37.2) between D2S335 and D2S126.The maximum lod score 3.19 (theta=0.0) was obtained in marker D2S325. Fine mapping shows that D2S2358～D2S2178 is the susceptible region whose hereditary distance was 2.21 cM. The genes responsible for leukonychia totalis remain uncertain, and there was no reported study on gene identification.Objective Hoping identify the potential gene mutation by gene screening in this pedigree with leukonychia totalis. Find the association between the genes and the disease of this family.Methods We chose the candidate genes including KLF7,CPO,LOC389071,and CREB1 in the susceptible region according to the function of gene and the tissue involved in the disease. Polymerase Chain Reaction (PCR) was used to amplification all exons and the frank regions of the four genes in the DNA of 2 patients and 2 sibs of the family in random. The direct sequencing was conducted to perform the mutation screen.Results Six sequence variances were found in KLF7,CPO,LOC389071, and CREB1 of this family: 42002G>A 206CTG→CTA in KLF7,20061 T>G 134 AGT→ AGG in CPO(S134R),21333A>T 188GCA→GCT in CPO,29525A>G in CPO,29660 A>G 316ACA→ACG in CPO,201775 A>G 102ACA→ACG in LOC389071. The result shows that the six variances were in either patients or sibs. Therefore the six single nucleotide polymorphisms (SNP) in the coding region of the candidate genes in this family aren't the gene mutation that caused the disease and no such mutation causing the disease was found.Conclusion The disease of the family with autosomal dominant hereditary leukonychia totalis were not caused by the mutation of exons and their flanking intronic sequences of KLF7 and CPO gene. Gene mutation analysis of other genes in the region will be put into practice.