Prospective Evaluation of Kidney Disease in Joubert Syndrome
Prospective Evaluation of Kidney Disease in Joubert Syndrome
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DOI：
10.2215/cjn.05660517
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发表时间：
2017-12-07
影响因子：
9.8
通讯作者：
Gunay-Aygun, Meral
中科院分区：
文献类型：
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作者：
Fleming, Leah R.;Doherty, Daniel A.;Gunay-Aygun, Meral
背景和目标 Joubert 综合征是一种与超过 30 个基因相关的遗传异质性纤毛病。肾脏疾病的特征和基因型-表型相关性尚未在单一中心的大型队列中进行评估。设计、设置、参与者和测量我们使用腹部超声检查、血液和尿液化学以及 DNA 测序对美国国立卫生研究院临床中心的 97 名 Joubert 综合征患者进行了评估。结果 患者年龄 0.6-36 岁（平均 9.0 +/- 7.6 岁）； 41 名女性。在 92 名患者的 19 个基因中发现了突变；三分之二的突变存在于六个基因中：TMEM67、C5orf42、CC2D2A、CEP290、AHI1 和 KIAA0586。 30% 的人检测出肾脏疾病，最常见与以下基因相关：CEP290（6 个基因中的 6 个）、TMEM67（22 个基因中的 11 个）和 AHI1（6 个基因中的 3 个）。在 C5orf42（15 例中的 0 例）或 KIAA0586（6 例中的 0 例）突变的患者中未发现肾脏疾病。 72% 的肾脏疾病患者的产前肾脏超声检查结果正常。肾脏疾病的具体类型包括肾结核（31%）、常染色体隐性多囊肾病/肾结核的重叠表型（35%）、单侧多囊性发育不良肾（10%）和不确定型囊性肾病（24%）。 24%的肾病患者出现早发性高血压。 ESRD 年龄 (n=13) 范围为 6 至 24 岁（平均 11.3 +/- 4.8 岁）。结论 多达三分之一的 Joubert 综合征患者患有肾脏疾病，最常见于 CEP290、TMEM67 和 AHI1 突变的患者。 C5orf42 或 KIAA0586 突变的患者患肾脏疾病的可能性较小。产前超声检查对于朱伯特综合征肾脏受累的预测效果不佳。单侧多囊性发育不良肾和常染色体隐性遗传性多囊肾病（如伴有早发性高血压的增大的肾脏）可能是 Joubert 综合征肾脏表型的一部分。
Background and objectives Joubert syndrome is a genetically heterogeneous ciliopathy associated with >30 genes. The characteristics of kidney disease and genotype-phenotype correlations have not been evaluated in a large cohort at a single center.Design, setting, participants, & measurements We evaluated 97 individuals with Joubert syndrome at the National Institutes of Health Clinical Center using abdominal ultrasonography, blood and urine chemistries, and DNA sequencing.Results Patients were ages 0.6-36 years old (mean of 9.0 +/- 7.6 years old); 41 were female. Mutations were identified in 19 genes in 92 patients; two thirds of the mutations resided in six genes: TMEM67, C5orf42, CC2D2A, CEP290, AHI1, and KIAA0586. Kidney disease was detected in 30%, most commonly in association with the following genes: CEP290 (six of six), TMEM67 (11 of 22), and AHI1 (three of six). No kidney disease was identified in patients with mutations in C5orf42 (zero of 15) or KIAA0586 (zero of six). Prenatal ultrasonography of kidneys was normal in 72% of patients with kidney disease. Specific types of kidney disease included nephronophthisis (31%), an overlap phenotype of autosomal recessive polycystic kidney disease/nephronophthisis (35%), unilateral multicystic dysplastic kidney (10%), and indeterminate-type cystic kidney disease (24%). Early-onset hypertension occurred in 24% of patients with kidney disease. Age at ESRD (n=13) ranged from 6 to 24 years old (mean of 11.3 +/- 4.8 years old).Conclusions Kidney disease occurs in up to one third of patients with Joubert syndrome, most commonly in those with mutations in CEP290, TMEM67, and AHI1. Patients with mutations in C5orf42 or KIAA0586 are less likely to develop kidney disease. Prenatal ultrasonography is a poor predictor of kidney involvement in Joubert syndrome. Unilateral multicystic dysplastic kidney and autosomal recessive polycystic kidney diseaselike enlarged kidneys with early-onset hypertension can be part of the Joubert syndrome kidney phenotype.