Linkage of a gene causing familial focal segmental glomerulosclerosis to chromosome 11 and further evidence of genetic heterogeneity
Linkage of a gene causing familial focal segmental glomerulosclerosis to chromosome 11 and further evidence of genetic heterogeneity
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DOI：
10.1006/geno.1999.5828
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发表时间：
1999-06-01
期刊：
影响因子：
4.4
通讯作者：
Vance, JM
中科院分区：
文献类型：
--
作者：
Winn, MP;Conlon, PJ;Vance, JM
局灶节段性肾小球硬化（FSGS）是一种以蛋白尿、肾病综合征和肾功能进行性丧失为特征的病理实体。它是终末期肾脏疾病（ESRD）的常见原因，最近，家族形式的FSGS已被确定。使用351个基因组微卫星标记对常染色体显性FSGS两个家族进行了连锁评价。对后续结果进行联动、多点分析和异质性检验。此外，还利用三个小家系进行单倍型分析。最大家族在11q21-q22染色体上发现连锁证据，最大负载评分为9.89。该基因目前定位于两侧标记D11S2002和D11S1986之间18厘米的区域。第二个家族的疾病与该位点或先前描述的染色体19q13上的位点无关。在三个较小的家庭中，受影响个体之间没有共享的单倍型。我们的研究结果表明，遗传异质性在FSGS中普遍存在，至少有三个基因导致FSGS表型。鉴定家族性FSGS的致病基因将为FSGS的分子基础和病理生理提供有价值的见解。(C) 1999学术出版社。
Focal segmental glomerulosclerosis (FSGS) is a pathological entity characterized by proteinuria, nephrotic syndrome, and the progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD), Recently, familial forms of FSGS have been identified. Two families with autosomal dominant FSGS were evaluated for linkage using 351 genomic microsatellite markers. Linkage, multipoint analysis, and tests for heterogeneity were performed on the subsequent results. In addition, three small families were used for haplotype analysis. Evidence for linkage was found on chromosome 11q21-q22 for the largest family, with a maximum lod score of 9.89. The gene is currently localized to an 18-cM area between flanking markers D11S2002 and D11S1986. The disease in a second family was not linked to this locus or to a previously described locus on chromosome 19q13. There were no shared haplotypes among affected individuals in the three smaller families. Our findings demonstrate that genetic heterogeneity is prevalent in FSGS in that at least three genes cause the FSGS phenotype. Identification of the genes that cause familial FSGS will provide valuable insights into the molecular basis and pathophysiology of FSGS. (C) 1999 Academic Press.