2012年11月23日 訊 /生物谷BIOON/ --一項(xiàng)新的由哥倫比亞大學(xué)醫(yī)學(xué)中心（CUMC）研究人員完成的研究證實(shí),，大約有10％出生時(shí)腎缺陷的孩子基因組存在很大改變,，而這些變化與神經(jīng)發(fā)育延遲和精神疾病有關(guān)。
這項(xiàng)研究結(jié)果發(fā)表在今天的American Journal of Human Genetics雜志上,，患者先天性腎臟疾病將被放置在亞組基因突變的基礎(chǔ)上來(lái)獲得更精確的診斷,。如果醫(yī)生發(fā)現(xiàn)孩子的腎臟畸形，這是一個(gè)警告標(biāo)志,，孩子可能有一個(gè)基因組疾病包括神經(jīng)發(fā)育延遲或精神疾病,。這是一個(gè)重大的影響來(lái)開(kāi)展個(gè)性化的醫(yī)療保健。
到現(xiàn)在為止,，還沒(méi)有研究針對(duì)先天性腎臟疾病與神經(jīng)紊亂的關(guān)系開(kāi)展,。新研究表明，在某些情況下,，神經(jīng)發(fā)育問(wèn)題可能歸因于相關(guān)基因組疾病,，而不是腎臟疾病，大約20％的腎缺陷是由DNA突變引起的,。
直到2000年代中期,，出現(xiàn)有效的技術(shù)用于檢測(cè)拷貝數(shù)變異時(shí)，科學(xué)家們認(rèn)為拷貝數(shù)變異只導(dǎo)致少數(shù)的健康障礙,。然后今天,，數(shù)以十萬(wàn)計(jì)的不同拷貝數(shù)變異被發(fā)現(xiàn)，并與幾種疾病包括孤獨(dú)癥,、精神分裂癥,、帕金森氏病等相關(guān)。為了探究查看是否拷貝數(shù)變異是參與先天性腎畸形， Gharavi博士等人掃描了522個(gè)人的基因組,，其中約17％的患者存在拷貝數(shù)變異,，而這些人又有腎臟疾病。
雖然目前還不清楚為什么腎臟畸形和神經(jīng)發(fā)育在某些情況下有關(guān)聯(lián),，但研究員猜測(cè)與腎臟發(fā)育有關(guān)的基因可能也參與大腦發(fā)育,。新研究還找了許多患者共同存在的幾個(gè)拷貝數(shù)變異，但同時(shí)也發(fā)現(xiàn)幾乎所有的患者都有獨(dú)特的拷貝數(shù)變異,，因此拷貝數(shù)變異不能成為臨床評(píng)估診斷標(biāo)準(zhǔn),。根據(jù)他們的結(jié)果，Gharavi士博和GSanna-Cherchi估計(jì),，可能有數(shù)百個(gè)不同的基因?qū)е孪忍煨阅I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.
