Intragenic duplication in the PKHD1 gene in autosomal recessive polycystic kidney disease.
Intragenic duplication in the PKHD1 gene in autosomal recessive polycystic kidney disease.
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DOI：
10.1186/s12881-015-0245-3
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发表时间：
2015-10-26
影响因子：
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通讯作者：
Fujii T
中科院分区：
文献类型：
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作者：
Miyazaki J;Ito M;Nishizawa H;Kato T;Minami Y;Inagaki H;Ohye T;Miyata M;Boda H;Kiriyama Y;Kuroda M;Sekiya T;Kurahashi H;Fujii T
在本研究中，我们报告了一对夫妇谁接受产前遗传诊断为常染色体隐性遗传性多囊肾病（ARPKD）。 这对健康的夫妇以前有一个健康的男孩，但经历了两个连续的新生儿死亡，由于呼吸窘迫造成的肺发育不良引起的羊水过少。这名妇女在意识到自己再次怀孕后咨询了我们的机构。我们立即通过对这对夫妇的样本进行靶外显子组测序，对PKHD 1基因进行了携带者检测。仅在父系等位基因中鉴定出致病性突变（c.9008C>T，p.S3003F）。通过对福尔马林固定、石蜡包埋的第二名新生儿患者肾组织的DNA进行桑格测序，证实了该突变，但在健康同胞中未发现。然后，我们使用分散在PKHD 1基因的微卫星标记进行单倍型分析。从子宫穿刺术中提取的DNA被确定属于一个携带者，这对夫妇决定继续怀孕，获得一个健康的新生儿。随后对外显子组数据的详细检查表明外显子45和46处的读取深度较高。多重连接依赖的探针扩增允许识别这两个外显子的重复。该病例提示了靶外显子组测序在ARPKD PKHD 1基因产前诊断中的潜在用途。这是首次报道ARPKD中PKHD 1基因的基因内重复。本文的在线版本（doi：10.1186/s12881-015-0245-3）包含补充材料，可供授权用户使用。
In the present study, we report on a couple who underwent prenatal genetic diagnosis for autosomal recessive polycystic kidney disease (ARPKD). This healthy couple had previously had a healthy boy but had experienced two consecutive neonatal deaths due to respiratory distress resulting from pulmonary hypoplasia caused by oligohydramnios. The woman consulted our facility after she realized she was pregnant again. We promptly performed a carrier test for the PKHD1 gene by target exome sequencing of samples from the couple. A pathogenic mutation was identified only in the paternal allele (c.9008C>T, p.S3003F). The mutation was confirmed by Sanger sequencing of the DNA from formalin-fixed, paraffin-embedded, kidney tissue of the second neonate patient and was not found in the healthy sibling. We then performed haplotype analyses using microsatellite markers scattered throughout the PKHD1 gene. DNA from the amniocentesis was determined to belong to a carrier, and the couple decided to continue with the pregnancy, obtaining a healthy newborn. Subsequent detailed examination of the exome data suggested higher read depth at exons 45 and 46. Multiplex ligation-dependent probe amplification allowed identification of duplication of these two exons. This case suggests the potential usefulness of target exome sequencing in the prenatal diagnosis of the PKHD1 gene in ARPKD. This is the first report of intragenic duplication in the PKHD1 gene in ARPKD. The online version of this article (doi:10.1186/s12881-015-0245-3) contains supplementary material, which is available to authorized users.