Gene Mutation Analysis In Chinese Pedigree With Hereditary Leukonychia Totalis

Hereditary leukonychia totalis is a very rare condition,which is an autosomal dominant disorder with variable penetrance.The genes responsible for leukonychia remain unkown,and there was no reported study on gene mapping and gene identification.Up to now,we have collected a Chinese pedigree with leukonychia totalis in HeBei province and draw a conclusion that the disease passed in the family is an autosomal dominant disorder.We have excluded keratin 17 as the susceptible gene.A whole genome scan in this Chinese family with leukonychia totalis hereditaris has been performed.Parametric linkage analyses identified that the region 2q32.3～2q37.2 between D2S335～D2S126 may harbor the susceptible genes.Fine mapping shows the marker D2S325 in this region achieved the maximum LOD score 3.19 (theta=0)and D2S2358～D2S2178 is the susceptible region whose hereditary distance is 2.13cM.In this region,we have analyzed the candidate genes including KLF7,CPO,LOC389071,CREB1,CRYGA,CRYGB,CRYGC,CRYGDand have not found the mutation genes connecting with leukonychia totalis hereditaris. Other genes will be selected from the susceptible region and analyzed in our study.Objective ToanalyzeFZD5(frizzled 5),LOC729607,FLJ40432,FAM119A gene mutation in a Chinese pedigree with autosomal dominant hereditary leukonychia totalis.Methods By means of polymerase chain reaction and direct sequencing,all 24 exons and their neighbouring intronic sequences of the four genes were analyzed to detect mutations.Results Eight mutations were found in all exons and their flanking intronic sequences of the four genes in the family.Namely 706 A→G in FZD5,.51661 absence of T and 57257 C→T and 71187 AG heterozygosis in LOC729607.26135 AG heterozygosis and 39784 AG heterozygosis in FLJ40432.11756 G→A and 11860 C→T in FAM119A.Since the variances could be find in the NCBI databank or in both patients and sibs sequences,the pathopoiesia mutation was not found.Conclusion The diseases of the family with autosomal dominant hereditary leukonychia totalis were not caused by the mutation of exons and their flanking intronic sequences of FZD5(frizzled 5),LOC729607,FLJ40432,FAM119A gene.