Mapping Of The Gene Responsible For Focal Segmental Glomerular Sclerosis In A Chinese Han Family

Objective:FSGS (focal segmental glomerusclerosis) is one of the commonest renal nephritis. The feature of FSGS is non-inflammatory sclerosis of part of renal capillary loops. Proteinuria and nephrotic syndrome are the main symptom of FSGS clinically. FFSGS (familial focal segmental glomerularsclerosis) is a special type of FSGS because several memebers in different generations could be affected FSGS in FFSGS family. The inheritance pattern of FFSGS can be autosomal dominant or autosomal recessive. Recently, Daskalakis had found that obout 18% FSGS were FFSGS. So it is crucial to find the causes of FSGS.Foreign scholars had proved that FFSGS was monogenic disorder. Loci of FFSGS in different races had been reported on 19q13,11q21-q22,6q12.3 and 1q25-q31. There are different gene loci and mutations for FFSGS in different races.We can find that responsible gene may locate in other chromosomals.Responsible gene for Chinese have not been found until now.We selected a Chinese family which has been identified FFSGS as the object of our research in order that we can find and clone the responsible gene of FFSGS. Methods:In this work, we studied a Chinese family with affected individuals in three generations and exhibited autosomal dominant kidney disease but no other systemic abnormalities. Blood samples were obtained and genomic DNA was extracted from peripheral blood leukocyte using conventional methods. DNA samples were amplified with three-temperature touchdown PCR. Genescan (version 3.7) and Genotyper (version 3.7) software packages (Perkin Elmer Corporation, USA) were used to generate genotypes. Data were calculated by two-point logarithm of odds LOD scores (Z), multipoint analysis and Haplotyping. Members of the family were firstly genotyped with microsatellite markers at loci associated with FFSGS on the reported regions of chromosomes. After exclusion of these loci, a genome-wide scan was performed. We made fine scan on the region identified by the genome-wide scan.Results:After giving the Chinese ethnic familial kidney disease family health examination and renal biopies to 2 members with proteinuria, we diagnosised FFSGS to this family. After exclusion of the loci repoted responsible for FFSGS( 19q13,11q21-q22,6q12.3 and 1q25-q31), a genome-wide scan was performed and significant evidence of linkage was obtained for marker D1S484 (Z=1.47(θ=0.00)). Haplotype data indicated a negative interval, but this locate attacted with the positive locate of the former FFSGS.Conclusions:1. Clinical screening,laboratory and pathology examination confirmed this family was FFSGS;2. The FFSGS family was autosomal dominant and anticipation could be found in the family;3. We can prove that FFSGS has genetic heterogeneity according to our initial result, following exclusion of the loci which had been reported;4. The locate of D1S484 is attacted with the positive locate of the former FFSGS.