Hou Ling, Du Yue, Zhang Mingming, Su Pengjun, Zhao Chengguang, Wu Yubin
Department of Pediatric Nephrology and Rheumatology, Shengjing Hospital of China Medical University Shenyang, China.
Department of Pathology, Shengjing Hospital of China Medical University Shenyang, China.
Int J Clin Exp Pathol. 2018 May 1;11(5):2869-2874. eCollection 2018.
: To report newly identified mutations in two families in China with cystic renal disease. : Two fetuses were found by prenatal ultrasound to have symmetrically enlarged kidneys with increased echogenicity and cystic changes. We isolated fetal and parental genomic DNAs from umbilical cord blood and circulating leukocytes, performed next generation sequencing for mutations, followed by Sanger sequencing for confirmation. We discovered two new heterozygous mutations in PKHD1: c.2507_2515delTGAAGGAGG (p.Val836_Glu838del) in exon 24 among the fetus and father, as well as c.6840G>A (p.Trp2280*) in exon 42 among the fetus and mother. A mutation of c.2507_2515delTGAAGGAGG caused deletion of three amino acids. Two heterozygous mutations in AHI1, c.1304G>A (p.Arg435Gln), and c.3257A>G (p.Glu1086Gly) were identified in the second fetus, while the former was also found in the mother. The mutated locus in AHI1 is highly conserved among humans, dogs, mice, and monkeys. : We report two newly identified mutations in PKHD1 and AHI1. An accurate genetic diagnosis is crucial for genetic counseling of parents with offspring carrying cystic renal disease.
报告中国两个患有囊性肾病家庭中新发现的突变。：产前超声检查发现两个胎儿双肾对称增大，回声增强且有囊性改变。我们从脐带血和循环白细胞中分离出胎儿及父母的基因组DNA，进行下一代测序寻找突变，随后通过桑格测序进行确认。我们在PKHD1基因中发现两个新的杂合突变：胎儿和父亲的第24外显子中的c.2507_2515delTGAAGGAGG（p.Val836_Glu838del），以及胎儿和母亲的第42外显子中的c.6840G>A（p.Trp2280*）。c.2507_2515delTGAAGGAGG突变导致三个氨基酸缺失。在第二个胎儿中鉴定出AHI1基因的两个杂合突变，c.1304G>A（p.Arg435Gln）和c.3257A>G（p.Glu1086Gly），其中前者在母亲中也被发现。AHI1基因的突变位点在人类、狗、小鼠和猴子中高度保守。：我们报告了PKHD1和AHI1基因中新发现的两个突变。准确的基因诊断对于患有携带囊性肾病后代的父母进行遗传咨询至关重要。
