title: A novel mutation identified in PKHD1 by targeted exome sequencing: guiding prenatal diagnosis for an ARPKD family.
abstract: Autosomal recessive polycystic kidney disease (ARPKD) is a rare hereditary renal cystic disease involving multiple organs, mainly the kidney and liver. Parents who had an affected child with ARPKD are in strong demand for an early and reliable prenatal diagnosis to guide the future pregnancies. Here we provide an example of prenatal diagnosis of an ARPKD family where traditional antenatal ultrasound examinations failed to produce conclusive results till 26th week of gestation. Compound heterozygous mutations c.274C>T (p.Arg92Trp) and c.9059T>C (p.Leu3020Pro) were identified using targeted exome sequencing in the patient and confirmed by Sanger sequencing. Further, the mother and father were revealed to be carriers of heterozygous c.274C>T and c.9059T>C mutations, respectively. Molecular prenatal diagnosis was performed for the current pregnancy by direct sequencing plus linkage analysis. Two mutations identified in the patient were both found in the fetus. In conclusion, compound heterozygous PKHD1 mutations were elucidated to be the molecular basis of the patient with ARPKD. The newly identified c.9059T>C mutation in the patient expands mutation spectrum in PKHD1 gene. For those ultrasound failed to provide clear diagnosis, we propose the new prenatal diagnosis procedure: first, screening underlying mutations in PKHD1 gene in the proband by targeted exome sequencing; then detecting causative mutations by direct sequencing in the fetal DNA and confirming results by linkage analysis.
authors.affiliation: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Jiang
authors.affiliation: Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of urinary Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Hong-Quan
authors.initials: HQ
authors.lastname: Gen
authors.affiliation: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors.forename: Ying-Wei
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Prenatal Diagnosis Center, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Genetics, Shanghai Institute of Pediatric Research, Shanghai, China. Electronic address: jxkshch@126.com.
authors.forename: Xing
authors.initials: X
authors.lastname: Ji
mesh_terms: D002675:Child, Preschool; D059472:Exome; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000000981:diagnostic imaging; D008040:Genetic Linkage; D005820:Genetic Testing / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D017044:Polycystic Kidney, Autosomal Recessive / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011956:Receptors, Cell Surface / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D014463:Ultrasonography
chemical_list: C451750:PKHD1 protein, human; D011956:Receptors, Cell Surface
keywords: ARPKD; Compound heterozygous mutation; PKHD1; Prenatal diagnosis; Targeted exome sequencing