Initial Mapping Of A Pedigree With A Chinese Family With Familial IgA Nephropathy

Objective:IgA nephropathy (IgAN) is one of the most common form of primary glomerulonephritis. It includes all kinds of clinical manifestations such as various degrees of hematuria, proteinuria, and the progressive loss of renal function. Familial IgA nephropathy is the special type of IgAN with autosomal dominant or X-linked recessive inheritance pattern. Its clinical manifestations are similar to the sporadic IgAN but with features such as higher morbility, worse prognosis and genetic anticipation. Many scholars find that the number of FIgAN patients is considerable and the responsible gene maybe different in different race according to the resultsof many large retrospective studies. Now, the chromosomal localization about FIgAN allover the world according to the literature is as follows, 2q36, 3p23-24, 4q26-31, 6q22-23, 17q12-22. And Lebanon researcher had repoted that he had identified responsible gene exclusive of the 2, 4, 6 chromosomal of the families which he studied in 2007. All the reports show that the responsible gene maybe locate others chromosomal. Responsible gene about Chinese FIgAN has not been report until now.We selected a Chinese family which has been identified FIgAN as the object of our research in order that we can find and clone the responsible gene of FIgAN.Methods:In this work, we studied a Chinese family with autosomal dominant kidney disease which has been identified as FIgAN according to the international standard. Blood samples of the family members were obtained and genomic DNA was extracted from peripheral blood leukocyte using conventional methods. We chose suitable microsatellite markers for the scan of genome. Firstly, we scanned the positions that had been reported responsible for FIgAN. The LOD score of these positions turned out to be negative; we subsequently scanned the whole genome. Data were analysed by two-point logarithm of odds LOD scores, multipoint analysis and Haplotyping.Results:Finished detailed and overall clinical examination of the family members, 6 patients received the renal biopsy, skin biopsy and electron microscope to furtherly identify the family as FIgAN. Members of the family were firstly genotyped with microsatellite markers at loci associated with FIgAN on the reported regions of chromosomes, but negative LOD scores were obtained. Following exclusion of these loci, a genome-wide scan was performed and significant evidence of linkage was obtained initially for marker D6S289, D6S422 and D6S1610 (Zmax=1.88(θ=0.00), Zmax=1.93(θ=0.00), Zmax=1.54(θ=0.01)). Haplotype data indicated a coralliform cataract disease gene in a 24-cM interval at a novel disease locus 6p21.2-6p23 between D6S289 and D6S1610. No genes related to Chinese FIgAN in this region have been reported so far.Conclusions:1. FIgAN can also exist in Chinese ethnic people.2. FIgAN family that we studied has the manner of inheritance with autosomal dominant and genetic anticipation .3. Following exclusion of the loci which had been reported, We can prove that FIgAN has the genetic heterogeneity according to our initial result.4. The locus of Chinese FIgAN is 6p21.2-6p23, and no genes related to Chinese FIgAN in this region have been reported so far.