Prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD):: Molecular genetics, clinical experience, and fetal morphology
Prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD):: Molecular genetics, clinical experience, and fetal morphology
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DOI：
10.1002/(sici)1096-8628(19980305)76:2
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发表时间：
1998-03-05
期刊：
影响因子：
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通讯作者：
Guay-Woodford, LM
中科院分区：
文献类型：
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作者：
Zerres, K;Mücher, G;Guay-Woodford, LM
常染色体隐性遗传性多囊肾病（ARPKD）是最常见的遗传性肾囊肿病之一，婴儿死亡率高。使用胎儿超声检查进行产前诊断是不可靠的，尤其是在妊娠早期。ARPKD位点已被定位到近端染色体6p，允许在“高危”家庭中进行基于单倍型的产前诊断。从1994年12月至1997年3月，我们收到了258份关于产前评估的咨询，我们已经完成了对212个家庭的分析。到目前为止，已在57个家庭中进行了65次产前分析。在大多数提出申请的家庭（45/57）中，索引儿童已经死亡，他们的DNA是从石蜡包埋的组织中提取的。18个胎儿为疾病相关单倍型纯合子。其中12例胎儿的病理解剖学检查显示典型的ARPKD改变，包括集合管扩张和特征性肝管板畸形。这些变化早在13周胎龄的两个胎儿中检测到。这些病例代表了迄今为止报告的ARPKD相关组织病理学的最早证明。一个高危胎儿被带到足月，结果没有受到影响。然而，ARPKD的诊断仍然可疑的索引患者。43个胎儿为非疾病相关单倍型的杂合子或纯合子，所有出生的婴儿在出生时表型未受影响。在4例中，侧翼标记之间发生重组事件，不可能进行基因型预测。其中3例妊娠终止，胎儿尸检证实为ARPKD，而1例胎儿足月分娩，出生时无异常。这些结果表明，基于单倍型的产前检测在ARPKD“高危”妊娠中是可行和可靠的。这些研究的绝对先决条件是对既往受累同胞的ARPKD进行准确诊断。(C)1998 Wiley-Liss，Inc.
Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common hereditary renal cystic diseases and has a high infant mortality. Prenatal diagnosis using fetal sonography can be unreliable, especially in early pregnancy. The ARPKD locus has been mapped to proximal chromosome 6p allowing haplotype-based prenatal diagnosis in "at-risk" families. From December 1994 to March 1997, we received 258 inquiries regarding prenatal evaluation and we have completed analyses in 212 families. To date, 65 prenatal analyses have been performed in 57 families. In the majority of the requesting families (45/57), the index children are deceased and their DNA was extracted from paraffin-embedded tissue. Eighteen fetuses were homozygous for the disease-associated haplotypes. In 12 of these fetuses, pathoanatomical examination demonstrated typical ARPKD changes consisting of dilated collecting ducts and the characteristic hepatic ductal plate malformation. These changes were detected in two fetuses as early as 13 weeks gestational age. These cases represent the earliest demonstration of ARPKD-associated histopathology reported to date. One high risk fetus was carried to term and turned out to be unaffected. However, the diagnosis of ARPKD remained doubtful in the index patient. Forty-three fetuses were either heterozygous or homozygous for a nondisease-associated haplotype and all infants born were phenotypically unaffected at birth. In four cases, a recombination event occurred between the flanking markers and no genotypic prediction was possible. Three of these pregnancies were terminated and necropsy of the fetuses confirmed ARPKD, while one fetus was carried to term and showed no abnormalities at birth.These results show that haplotype-based prenatal testing is feasible and reliable in pregnancies "at risk" for ARPKD. An absolute prerequisite for these studies is an accurate diagnosis of ARPKD in previously affected sib(s). (C) 1998 Wiley-Liss, Inc.