NUP107 mutations in children with steroid-resistant nephrotic syndrome
NUP107 mutations in children with steroid-resistant nephrotic syndrome
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DOI：
10.1093/ndt/gfw103
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发表时间：
2017-06-01
影响因子：
6.1
通讯作者：
Cheong, Hae Il
中科院分区：
文献类型：
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作者：
Park, Eujin;Ahn, Yo Han;Cheong, Hae Il
背景：NUP107 是一种与儿童常染色体隐性遗传性类固醇抵抗性肾病综合征 (SRNS) 伴局灶节段性肾小球硬化 (FSGS) 相关的新基因。 SR-FSGS 儿童中 NUP107 突变的频率仍不清楚。方法：招募了 9 个有两个兄弟姐妹受儿童期发病 SRNS 或蛋白尿影响的家庭。所有家庭中至少一名受影响的兄弟姐妹通过肾活检证实了 FSGS。此外，还纳入了 69 名经活检证实为 SR-FSGS 且对任何治疗均无反应的散发儿科病例。使用聚合酶链反应扩增 NUP107 基因侧翼内含子的所有编码外显子并直接测序。结果：在家族病例的四对 (44.4%) 兄弟姐妹和三对 (4.3%) 散发病例中检测到双等位基因 NUP107 突变。所有受影响的患者都在一个等位基因中携带 p.Asp831Ala 突变，在另一个等位基因中携带截短或异常剪接突变。与突变阴性患者相比，NUP107 突变阳性患者的发病年龄较早（39.4 +/- 13.1 个月 vs 76.8 +/- 50.0 个月，P= 0.027），进展至终末期肾病的速度更快（年龄为 58.9 +/- 23.4 个月 vs 123.1 +/- 62.7 个月，P < 0.001）。接受肾移植的 8 例突变阳性病例中，无一例在移植肾中出现 FSGS 复发，而突变阴性病例中有 35.3% 出现 FSGS 复发。结论：在韩国 SR-FSGS 儿童中观察到 NUP107 突变的发生率出乎意料地高。 SR-FSGS 儿童的初始基因筛查应包括 NUP107 基因，至少在韩国如此。需要进一步研究来确定其他国家 NUP107 突变的发生率。
Background: NUP107 is a novel gene associated with autosomal recessive steroid-resistant nephrotic syndrome (SRNS) with focal segmental glomerulosclerosis (FSGS) in children. The frequency of NUP107 mutations in children with SR-FSGS remains unknown.Methods: Nine families with two siblings affected by childhood-onset SRNS or proteinuria were recruited. FSGS was confirmed by a kidney biopsy in at least one affected sibling in all families. Additionally, 69 sporadic pediatric cases with biopsy-proven SR-FSGS who had not responded to any treatment were included. All coding exons with flanking introns of the NUP107 gene were amplified using polymerase chain reaction and directly sequenced.Results: Biallelic NUP107 mutations were detected in four pairs (44.4%) of siblings from the familial cases and three (4.3%) sporadic cases. All affected patients harbored the p.Asp831Ala mutation in one allele and a truncating or abnormal splicing mutation in the other allele. NUP107 mutation-positive patients showed an earlier onset age (39.4 +/- 13.1 versus 76.8 +/- 50.0 months, P= 0.027) and more rapid progression to end-stage renal disease (at the ages of 58.9 +/- 23.4 versus 123.1 +/- 62.7 months, P < 0.001) compared with mutation-negative patients. None of the eight mutation-positive cases, who underwent kidney transplantation, showed recurrence of FSGS in the graft kidney, while 35.3% of mutation-negative cases showed recurrence of FSGS.Conclusions: An unexpectedly high incidence of NUP107 mutations was observed in Korean children with SR-FSGS. Initial genetic screening of children with SR-FSGS should include the NUP107 gene, at least in Korea. Further studies are necessary to determine the incidences of NUP107 mutations in other countries.