A novel mutation identified in PKHD1 by targeted exome sequencing: guiding prenatal diagnosis for an ARPKD family.
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.
['Xu|Yan|Y|', 'Xiao|Bing|B|', 'Jiang|Wen-Ting|WT|', 'Wang|Lei|L|', 'Gen|Hong-Quan|HQ|', 'Chen|Ying-Wei|YW|', 'Sun|Yu|Y|', 'Ji|Xing|X|']
D002675:Child, Preschool D059472:Exome D005260:Female D005315:Fetal Diseases D008040:Genetic Linkage D005820:Genetic Testing D006579:Heterozygote D006801:Humans D008297:Male D009154:Mutation D017044:Polycystic Kidney, Autosomal Recessive D011247:Pregnancy D011296:Prenatal Diagnosis D011956:Receptors, Cell Surface D017422:Sequence Analysis, DNA D014463:Ultrasonography
PKHD1 Targeted exome sequencing Prenatal diagnosis ARPKD Compound heterozygous mutation