Evaluating Mendelian nephrotic syndrome genes for evidence for risk alleles or oligogenicity that explain heritability
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- 作者：Brendan D. Crawford ; Christopher E. Gillies ; Catherine C. Robertson…
- 关键词：Nephrotic syndrome ; Variant ; Mendelian ; Oligogenicity ; Risk allele
- 刊名：Pediatric Nephrology
- 出版年：2017
- 出版时间：March 2017
- 年：2017
- 卷：32
- 期：3
- 页码：467-476
- 全文大小：
- 刊物类别：Medicine
- 刊物主题：Pediatrics; Nephrology; Urology;
- 出版者：Springer Berlin Heidelberg
- ISSN：1432-198X
- 卷排序：32
文摘
BackgroundMore than 30 genes can harbor rare exonic variants sufficient to cause nephrotic syndrome (NS), and the number of genes implicated in monogenic NS continues to grow. However, outside the first year of life, the majority of affected patients, particularly in ancestrally mixed populations, do not have a known monogenic form of NS. Even in those children classified with a monogenic form of NS, there is phenotypic heterogeneity. Thus, we have only discovered a fraction of the heritability of NS—the underlying genetic factors contributing to phenotypic variation. Part of the “missing heritability” for NS has been posited to be explained by patients harboring coding variants across one or more previously implicated NS genes, insufficient to cause NS in a classical Mendelian manner, but that nonetheless have a sufficient impact on protein function to cause disease. However, systematic evaluation in patients with NS for rare or low-frequency risk alleles within single genes, or in combination across genes (“oligogenicity”), has not been reported. To determine whether, compared with a reference population, patients with NS have either a significantly increased burden of protein-altering variants (“risk-alleles”), or a unique combination of them (“oligogenicity”), in a set of 21 genes implicated in Mendelian forms of NS.