Clinical and genetic heterogeneity in familial focal segmental glomerulosclerosis. International Collaborative Group for the Study of Familial Focal Segmental Glomerulosclerosis.
Clinical and genetic heterogeneity in familial focal segmental glomerulosclerosis. International Collaborative Group for the Study of Familial Focal Segmental Glomerulosclerosis.
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DOI：
10.1046/j.1523-1755.1999.00384.x
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发表时间：
1999-04
影响因子：
19.6
通讯作者：
M. Winn;Peter J. Conlon;Kelvin L. Lynn;David N. Howell;D. A. Gross;A. Rogala;Anne H. Smith;Felicia L. Graham;M. Bembe;L. D. Quarles;M. Pericak-Vance;Jeffery M. Vance
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文献类型：
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作者：
M. Winn;Peter J. Conlon;Kelvin L. Lynn;David N. Howell;D. A. Gross;A. Rogala;Anne H. Smith;Felicia L. Graham;M. Bembe;L. D. Quarles;M. Pericak-Vance;Jeffery M. Vance
局灶节段性肾小球硬化症（FFSGS）的家族性表现为常染色体显性或隐性遗传。这些遗传形式的FSGS的遗传基础是未知的。最近一项对来自俄克拉荷马州的一个常染色体显性FSGS家族的研究将这种疾病与染色体19 q的一个区域联系起来。此外，染色体19 q13上该区域的基因多态性与芬兰型先天性肾病综合征有关。我们已经确定和特点的一个大家庭与常染色体显性FFSGS（杜克6530）。方法比较家系的临床和遗传异质性。为了检测我们家族与19号染色体的这一部分的连锁，从102个家族成员中分离出基因组DNA，并使用跨越19号染色体上感兴趣区域的8个微卫星标记进行聚合酶链反应。采用两点连锁分析、多点分析和混合物试验对数据进行评价。结果连锁被排除在距离+/-5至10厘米的所有标记物测试与两点log 10的几率连锁（LOD）评分，并从一个约60厘米的间隔在该地区的染色体19 q通过多点分析。结论FSGS是一种常见的病理表现，病因多样，被称为肾小球损伤的“最终共同途径”。这种多样性可能与我们已经建立的遗传异质性相关。因此，我们的数据表明，至少有两个基因负责这种疾病，并有遗传以及临床异质性常染色体显性FSGS。
BACKGROUND Familial forms of focal segmental glomerulosclerosis (FFSGS) that exhibit autosomal dominant or recessive patterns of inheritance have been described. The genetic basis of these hereditary forms of FSGS is unknown. One recent study of a kindred from Oklahoma with an autosomal dominant form of FSGS linked this disease to a region of chromosome 19q. In addition, polymorphisms in a gene in this region on chromosome 19q13 have been linked to congenital nephrotic syndrome of the Finnish type. We have ascertained and characterized a large family with autosomal dominant FFSGS (Duke 6530). METHODS Families were compared for clinical and genetic heterogeneity. To test for linkage of our family to this portion of chromosome 19, genomic DNA was isolated from 102 family members, and polymerase chain reaction was performed using eight microsatellite markers that spanned the area of interest on chromosome 19. Data were evaluated using two-point linkage analysis, multipoint analysis, and an admixture test. RESULTS Linkage was excluded at a distance of +/- 5 to 10 CM for all markers tested with two-point log10 of the odds of linkage (LOD) scores and from an approximate 60 CM interval in this area of chromosome 19q via multipoint analysis. CONCLUSIONS FSGS has been called the "final common pathway" of glomerular injury, as it is a frequent pathological manifestation with diverse etiologies. This diversity likely correlates with the genetic heterogeneity that we have established. Thus, our data demonstrate that there are at least two genes responsible for this disease, and there is genetic as well as clinical heterogeneity in autosomal dominant FSGS.