Homonucleotide expansion and contraction mutations of PAX2 and inclusion of Chiari 1 malformation as part of renal-coloboma syndrome.
Homonucleotide expansion and contraction mutations of PAX2 and inclusion of Chiari 1 malformation as part of renal-coloboma syndrome.
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PAX2 的同核苷酸扩张和收缩突变以及 Chiari 1 畸形作为肾缺损综合征的一部分。
DOI：
10.1002/(sici)1098-1004(199911)14:5
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Dobyns,WB
中科院分区：
文献类型：
--
作者：
Schimmenti,LA;Shim,HH;Wirtschafter,JD;Panzarino,VA;Kashtan,CE;Kirkpatrick,SJ;Wargowski,DS;France,TD;Michel,E;Dobyns,WB
肾结肠瘤综合征是一种常染色体显性遗传病，其特征为结肠状眼缺陷、膀胱输尿管反流和肾脏异常，由pax2基因突变引起。本研究的目的是鉴定pax2的突变并了解相关的患者表型。我们报告了一个严重感染的女孩和一个轻度感染的母亲和女儿，他们都有pax2同型鸟嘌呤道（7g）错义突变。母亲和女儿有视神经结肠瘤，女儿有膀胱输尿管反流。受严重影响的女孩发展为肾功能衰竭和双侧结肠性眼部缺损。此外，这名女孩还出现了脑积水，并伴有扁平肌和Chiari 1型畸形。我们通过SSCP和测序检测了这些个体的基因组DNA。这对母女发生了一种新的突变：pax2的一个等位基因的7个G到6个G的序列收缩，导致下游两个氨基酸的过早终止密码子。受严重影响的女孩扩增到8g，导致下游27个氨基酸过早停止密码子。在其他无脑异常的患者中也发现了8g扩张，并在小鼠模型PAX21Neu中自发发生。我们将已知的与pax2突变相关的表型扩展到包括脑畸形。pax2中的同型鸟嘌呤通道是自发扩张或收缩突变的热点，证明了同型核苷酸通道突变在人类畸形综合征中的重要性。[j] .农业科学，1999。©1999 Wiley‐Liss, Inc。
Renal‐Coloboma syndrome, an autosomal dominant disorder characterized by colobomatous eye defects, vesicoureteral reflux, and abnormal kidneys, results from mutations inPAX2. The purpose of this study was to identify mutations inPAX2and understand the associated patient phenotypes. We report a severely affected girl and a mildly affected mother and daughter, all of whom havePAX2homoguanine tract (7 G) missense mutations. The mother and daughter have optic nerve colobomas and the daughter has vesicoureteral reflux. The severely affected girl developed renal failure and has bilateral colobomatous eye defects. Additionally, this girl developed hydrocephalus associated with platybasia and a Chiari 1 malformation. We examined genomic DNA from these individuals by SSCP and sequencing. The mother and daughter had a novel mutation: a contraction in a string of 7 G's to 6 G's in one allele ofPAX2, leading to a premature stop codon two amino acids downstream. The severely affected girl had an expansion to 8 G's, leading to a premature stop codon 27 amino acids downstream. The 8 G expansion has been found in other patients without brain anomalies and has occurred spontaneously in a mouse model,PAX21Neu. We expand the known phenotype associated with mutations inPAX2to include brain malformations. The homoguanine tract inPAX2is a hot spot for spontaneous expansion or contraction mutations and demonstrates the importance of homonucleotide tract mutations in human malformation syndromes. Hum Mutat 14:369–376, 1999. © 1999 Wiley‐Liss, Inc.