全外显子组测序揭示一个导致儿科患者肾单位肾痨的 XPNPEP3 新突变。
Whole Exome Sequencing Reveals a XPNPEP3 Novel Mutation Causing Nephronophthisis in a Pediatric Patient.
机构信息
Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Medical Genetics, Schools of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
出版信息
Iran Biomed J. 2020 Nov;24(6):405-8. doi: 10.29252/ibj.24.6.400. Epub 2020 May 31.
BACKGROUND
Nephronophthisis (NPHP) is a progressive tubulointestinal kidney condition that demonstrates an AR inheritance pattern. Up to now, more than 20 various genes have been detected for NPHP, with NPHP1 as the first one detected. X-prolyl aminopeptidase 3 (XPNPEP3) mutation is related to NPHP-like 1 nephropathy and late onset NPHP.
METHODS
The proband (index patient) had polyuria, polydipsia and chronic kidney disease and was clinically suspected of NPHP. After the collection of blood sample from proband and her parents, whole exome sequencing (WES) was performed to identify the possible variants in the proband from a consanguineous marriage. The functional importance of variants was estimated by bioinformatic analysis. In the affected proband and her parents, Sanger sequencing was conducted for variants’ confirmation and segregation analysis.
RESULTS
Clinical and paraclinical investigations of the patient was not informative. Using WES, we could detect a novel homozygous frameshift mutation in XPNPEP3 (NM_022098.2: c.719_720insA; p. Q241Tfs*13), and by Sanger sequencing, we demonstrated an insertion in XPNPEP3.
CONCLUSION
The homozygous genotype of the novel p.Q241Tfs*31 variant in XPNPEP3 may cause NPHP in the early childhood age.
背景
肾髓质囊性病（NPHP）是一种进行性的肾小管肠肾病，表现为 AR 遗传模式。到目前为止，已经发现了超过 20 种不同的 NPHP 基因，其中 NPHP1 是第一个被发现的。X-脯氨酰氨基肽酶 3（XPNPEP3）突变与 NPHP 样肾病和晚发性 NPHP 有关。
方法
先证者（索引患者）有多尿、多饮和慢性肾脏病，临床上疑似 NPHP。在采集先证者及其父母的血液样本后，对来自近亲婚配的先证者进行全外显子组测序（WES），以鉴定可能的变异。通过生物信息学分析评估变异的功能重要性。在受影响的先证者及其父母中，对变异进行 Sanger 测序以进行确认和遗传分析。
结果
患者的临床和辅助检查结果无明显异常。通过 WES，我们可以检测到 XPNPEP3 中的一个新的纯合移码突变（NM_022098.2: c.719_720insA;p.Q241Tfs*13），并通过 Sanger 测序证实 XPNPEP3 中的插入。
结论
XPNPEP3 中新型 p.Q241Tfs*31 变异的纯合基因型可能导致儿童早期的 NPHP。
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