Incompletely Penetrant PKD1 Alleles Mimic the Renal Manifestations of ARPKD
Incompletely Penetrant PKD1 Alleles Mimic the Renal Manifestations of ARPKD
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DOI：
10.1681/asn.2009101070
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发表时间：
2010-07-01
影响因子：
13.6
通讯作者：
Harris, Peter C.
中科院分区：
文献类型：
--
作者：
Vujic, Mihailo;Heyer, Christina M.;Harris, Peter C.
常染色体显性多囊肾病（ADPKD），由PKD1或PKD2突变引起，通常是一种成人发病的疾病，但很少表现为以典型的ADPKD为特征的家庭中的新生儿疾病。反式中的PKD1等位基因与失活的PKD1等位基因共遗传是导致早发性ADPKD的机制之一。在这里，我们描述了两个没有囊性肾病史的家系，每个家系都包含两个在子宫内发病的大量PKD患者。这些表现是典型的常染色体隐性PKD (ARPKD)，但它们与已知的ARPKD基因PKHD1无关。ADPKD基因的突变分析提供了强有力的证据，表明两个家族都遗传了两个不完全渗透的PKD1等位基因。这些患者表明，PKD1突变可以表现为肾脏累及的ARPKD的表型，并强调了在没有PKHD1阳性突变数据的ARPKD中基于连锁诊断的危险。此外，由不完全渗透的PKD1等位基因导致的ARPKD和这些患者之间的表型重叠支持了这些疾病的共同发病机制。
Autosomal dominant polycystic kidney disease (ADPKD), caused by mutation in PKD1 or PKD2, is usually an adult-onset disorder but can rarely manifest as a neonatal disease within a family characterized by otherwise typical ADPKD. Coinheritance of a hypomorphic PKD1 allele in trans with an inactivating PKD1 allele is one mechanism that can cause early onset ADPKD. Here, we describe two pedigrees without a history of cystic kidney disease that each contain two patients with onset of massive PKD in utero. The presentations were typical of autosomal recessive PKD (ARPKD) but they were not linked to the known ARPKD gene, PKHD1. Mutation analysis of the ADPKD genes provided strong evidence that both families inherited, in trans, two incompletely penetrant PKD1 alleles. These patients illustrate that PKD1 mutations can manifest as a phenocopy of ARPKD with respect to renal involvement and highlight the perils of linkage-based diagnostics in ARPKD without positive PKHD1 mutation data Furthermore, the phenotypic overlap between ARPKD and these patients resulting from incomplete penetrant PKD1 alleles support a common pathogenesis for these diseases.