2012年11月23日 讯 /生物谷BIOON/ --一项新的由哥伦比亚大学医学中心（CUMC）研究人员完成的研究证实，大约有10％出生时肾缺陷的孩子基因组存在很大改变，而这些变化与神经发育延迟和精神疾病有关。
这项研究结果发表在今天的American Journal of Human Genetics杂志上，患者先天性肾脏疾病将被放置在亚组基因突变的基础上来获得更精确的诊断。如果医生发现孩子的肾脏畸形，这是一个警告标志，孩子可能有一个基因组疾病包括神经发育延迟或精神疾病。这是一个重大的影响来开展个性化的医疗保健。
到现在为止，还没有研究针对先天性肾脏疾病与神经紊乱的关系开展。新研究表明，在某些情况下，神经发育问题可能归因于相关基因组疾病，而不是肾脏疾病，大约20％的肾缺陷是由DNA突变引起的。
直到2000年代中期，出现有效的技术用于检测拷贝数变异时，科学家们认为拷贝数变异只导致少数的健康障碍。然后今天，数以十万计的不同拷贝数变异被发现，并与几种疾病包括孤独症、精神分裂症、帕金森氏病等相关。为了探究查看是否拷贝数变异是参与先天性肾畸形， Gharavi博士等人扫描了522个人的基因组，其中约17％的患者存在拷贝数变异，而这些人又有肾脏疾病。
虽然目前还不清楚为什么肾脏畸形和神经发育在某些情况下有关联，但研究员猜测与肾脏发育有关的基因可能也参与大脑发育。新研究还找了许多患者共同存在的几个拷贝数变异，但同时也发现几乎所有的患者都有独特的拷贝数变异，因此拷贝数变异不能成为临床评估诊断标准。根据他们的结果，Gharavi士博和GSanna-Cherchi估计，可能有数百个不同的基因导致先天性肾畸形。（生物谷：Bioon.com）
doi:10.1016/j.ajhg.2012.10.007
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Copy-Number Disorders Are a Common Cause of Congenital Kidney Malformations
Simone Sanna-Cherchi, Krzysztof Kiryluk, Katelyn E. Burgess, Monica Bodria, Matthew G. Sampson, Dexter Hadley, Shannon N. Nees, Miguel Verbitsky, Brittany J et al.
We examined the burden of large, rare, copy-number variants (CNVs) in 192 individuals with renal hypodysplasia (RHD) and replicated findings in 330 RHD cases from two independent cohorts. CNV distribution was significantly skewed toward larger gene-disrupting events in RHD cases compared to 4,733 ethnicity-matched controls (p = 4.8 1011). This excess was attributable to known and novel (i.e., not present in any database or in the literature) genomic disorders. All together, 55/522 (10.5%) RHD cases harbored 34 distinct known genomic disorders, which were detected in only 0.2% of 13,839 population controls (p = 1.2 1058). Another 32 (6.1%) RHD cases harbored large gene-disrupting CNVs that were absent from or extremely rare in the 13,839 population controls, identifying 38 potential novel or rare genomic disorders for this trait. Deletions at the HNF1B locus and the DiGeorge/velocardiofacial locus were most frequent. However, the majority of disorders were detected in a single individual. Genomic disorders were detected in 22.5% of individuals with multiple malformations and 14.5% of individuals with isolated urinary-tract defects; 14 individuals harbored two or more diagnostic or rare CNVs. Strikingly, the majority of the known CNV disorders detected in the RHD cohort have previous associations with developmental delay or neuropsychiatric diseases. Up to 16.6% of individuals with kidney malformations had a molecular diagnosis attributable to a copy-number disorder, suggesting kidney malformations as a sentinel manifestation of pathogenic genomic imbalances. A search for pathogenic CNVs should be considered in this population for the diagnosis of their specific genomic disorders and for the evaluation of the potential for developmental delay.
