Cason Rachel K, Williams Anna, Chryst-Stangl Megan, Wu Guanghong, Huggins Kinsie, Brathwaite Kaye E, Lane Brandon M, Greenbaum Larry A, D'Agati Vivette D, Gbadegesin Rasheed A
Division of Nephrology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States.
Division of Pediatric Nephrology, Children's Hospital at Montefiore, The Bronx, NY, United States.
Front Pediatr. 2022 Jul 7;10:915174. doi: 10.3389/fped.2022.915174. eCollection 2022.
Focal segmental glomerulosclerosis (FSGS) is a major cause of end stage kidney disease, with the collapsing form having the worst prognosis. Study of families with hereditary FSGS has provided insight into disease mechanisms.
In this report, we describe a sibling pair with mutations and collapsing FSGS (cFSGS). For each brother, we performed next generation sequencing and segregation analysis by direct sequencing. To determine if the variants found in the index family are a common cause of cFSGS, we screened 7 patients with cFSGS, gleaned from our cohort of 200 patients with FSGS, for variants in as well as for high-risk genotypes.
We identified segregating compound heterozygous variants > > in the two brothers. We did not find any pathogenic variants in the seven patients with cFSGS from our cohort, and as expected five of these seven patients carried the high-risk genotype.
To the best of our knowledge, this is the first report of cFSGS in patients with mutations, based on this report, mutations in and other nucleoporin genes should be considered when evaluating a child with familial cFSGS. Determining the mechanisms by which these variants cause cFSGS may provide insight into the pathogenesis of the more common primary and virus-mediated forms of cFSGS.
局灶节段性肾小球硬化（FSGS）是终末期肾病的主要病因，其中塌陷型预后最差。对遗传性FSGS家族的研究为疾病机制提供了深入了解。
在本报告中，我们描述了一对患有突变和塌陷型FSGS（cFSGS）的同胞兄弟。对于每个兄弟，我们通过直接测序进行了下一代测序和分离分析。为了确定在索引家族中发现的变异是否是cFSGS的常见病因，我们从我们的200例FSGS患者队列中筛选了7例cFSGS患者，检测其基因变异以及高风险基因型。
我们在两兄弟中鉴定出分离的复合杂合基因变异。我们在队列中的7例cFSGS患者中未发现任何致病变异，正如预期的那样，这7例患者中有5例携带高风险基因型。
据我们所知，这是首次报道有基因突变的患者发生cFSGS，基于本报告，在评估家族性cFSGS患儿时应考虑基因及其他核孔蛋白基因突变。确定这些变异导致cFSGS的机制可能有助于深入了解更常见的原发性和病毒介导形式的cFSGS的发病机制。
