PAX2 Mutations in Fetal Renal Hypodysplasia
PAX2 Mutations in Fetal Renal Hypodysplasia
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DOI：
10.1002/ajmg.a.33133
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发表时间：
2010-04-01
影响因子：
2
通讯作者：
Gubler, Marie-Claire
中科院分区：
文献类型：
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作者：
Martinovic-Bouriel, Jelena;Benachi, Alexandra;Gubler, Marie-Claire
乳头肾综合征也称为肾缺损综合征（OMIM 120330）是一种常染色体显性遗传疾病，包括视神经异常和肾少巨肾发育不全。这种伴随代偿性肾小球肥大的肾单位生成数量减少导致慢性肾功能不全伴肾衰竭。我们报告了两个分别在妊娠24周和18周时出现PAX 2突变的胎儿，他们出生于两个不同的兄弟姐妹。在我们的第一个病人，终止妊娠被选为羊水过少和怀疑肾发育不全的健康夫妇与不显着的以往的临床病史。该胎仔双侧肾脏不对称异常，包括一个小的多囊性左肾和一个极度发育不全的右肾。组织学检查显示左肾发育异常，而发育不良的右肾组织相当正常。眼科检查发现双侧视神经缺损。这些异常的关联，高度提示乳头肾综合征，导致我们进行PAX 2基因的分子研究。PAX 2编码序列的直接测序鉴定了PAX 2外显子3中核苷酸935的从头单个G缺失，导致移码突变（c.392 delG，p.Ser131 Thrfs（星星）28）。在第二个家庭中，母系遗传的PAX 2突变的存在导致了终止妊娠的决定。孕18周的胎儿出现乳头肾综合征，包括肾发育不良和视神经缺损。为了解决PAX 2参与孤立性肾脏“疾病”的问题，筛选了18例符合标准的胎儿：10/18例单侧或双侧发育不全，6/18例双侧多囊性发育不良伴肾脏增大，2/18例经胎儿病理学检查证实双侧重度发育不全。据我们所知，我们的第一个病人是一个未报告的胎儿乳头肾综合征的诊断，和另一个例子的影响，定向胎儿病理学检查的遗传咨询的父母。(C)2010 Wiley-Liss，Inc.
Papillorenal syndrome also known as renal-coloboma syndrome (OMIM 120330) is an autosomal dominant condition comprising optic nerve anomaly and renal oligomeganephronic hypoplasia. This reduced number of nephron generations with compensatory glomerular hypertrophy leads towards chronic insufficiency with renal failure. We report on two fetuses with PAX2 mutations presenting at 24 and 18 weeks' gestation, respectively, born into two different sibships. In our first patient, termination of pregnancy was elected for anhydramnios and suspicion of renal agenesis in the healthy couple with an unremarkable previous clinical history. This fetus had bilateral asymmetric kidney anomalies including a small multicystic left kidney, and an extremely hypoplastic right kidney. Histology showed dysplastic lesions in the left kidney, contrasting with rather normal organization in the hypoplastic right kidney. Ocular examination disclosed bilateral optic nerve coloboma. The association of these anomalies, highly suggestive of the papillorenal syndrome, led us to perform the molecular study of the PAX2 gene. Direct sequencing of the PAX2 coding sequence identified a de novo single G deletion of nucleotide 935 in exon 3 of the PAX2 resulting in a frameshift mutation (c.392delG, p.Ser131Thrfs(star)28). In the second family, the presence of a maternally inherited PAX2 mutation led to a decision for termination of pregnancy. The 18-week gestation fetus presented the papillorenal syndrome including hypoplastic kidneys and optic nerve coloboma. In order to address the PAX2 involvement in isolated renal "disease," 18 fetuses fulfilling criteria were screened: 10/18 had uni- or bilateral agenesis, 6/18 had bilateral multicystic dysplasia with enlarged kidneys, and 2/18 presented bilateral severe hypodysplasia confirmed on fetopathological examination. To the best of our knowledge, our first patient represents an unreported fetal diagnosis of papillorenal syndrome, and another example of the impact of oriented fetopathological examination in genetic counseling of the parents. (C) 2010 Wiley-Liss, Inc.