Fourteen Monogenic Genes Account for 15% of Nephrolithiasis/Nephrocalcinosis
Fourteen Monogenic Genes Account for 15% of Nephrolithiasis/Nephrocalcinosis
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DOI：
10.1681/asn.2014040388
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发表时间：
2015-03-01
影响因子：
13.6
通讯作者：
Hildebrandt, Friedhelm
中科院分区：
文献类型：
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作者：
Halbritter, Jan;Baum, Michelle;Hildebrandt, Friedhelm
肾结石是一种发病率很高的常见疾病。尽管已经确定了数十种单基因原因，但单基因疾病的比例尚未得到充分研究。为了确定可以通过 30 个已知肾结石基因中的 1 个突变进行分子解释的病例百分比，我们对一组从典型肾结石诊所连续招募的患者进行了高通量突变分析。该队列由来自 268 个患有肾结石 (n = 256) 或孤立性肾钙质沉着症 (n = 16) 家庭的 272 名遗传未解决的个体（106 名儿童和 166 名成人）组成。我们在 30 个分析基因中的 14 个中检测到了 50 个可能的致病突变，从而对所有病例中的 14.9%（268 个病例中的 40 个）进行了分子诊断；检测到的 50 个突变中有 20 个是新突变（40%）。胱氨酸尿症基因 SLC7A9 (n=19) 突变最频繁。单基因病例的百分比在成人（11.4%）和儿童队列（20.8%）中均显着较高。隐性原因在儿童中更为常见，而显性疾病在成人中更为常见。我们的研究对肾结石疾病的单基因原因进行了深入分析。我们认为，了解肾结石和肾钙质沉着症的分子原因可能具有实际意义，并可能有助于个性化治疗。
Nephrolithiasis is a prevalent condition with a high morbidity. Although dozens of monogenic causes have been identified, the fraction of single-gene disease has not been well studied. To determine the percentage of cases that can be molecularly explained by mutations in 1 of 30 known kidney stone genes, we conducted a high-throughput mutation analysis in a cohort of consecutively recruited patients from typical kidney stone clinics. The cohort comprised 272 genetically unresolved individuals (106 children and 166 adults) from 268 families with nephrolithiasis (n=256) or isolated nephrocalcinosis (n=16). We detected 50 likely causative mutations in 14 of 30 analyzed genes, leading to a molecular diagnosis in 14.9% (40 of 268) of all cases; 20 of 50 detected mutations were novel (40%). The cystinuria gene SLC7A9 (n=19) was most frequently mutated. The percentage of monogenic cases was notably high in both the adult (11.4%) and pediatric cohorts (20.8%). Recessive causes were more frequent among children, whereas dominant disease occurred more abundantly in adults. Our study provides an in-depth analysis of monogenic causes of kidney stone disease. We suggest that knowledge of the molecular cause of nephrolithiasis and nephrocalcinosis may have practical implications and might facilitate personalized treatment.