Intragenic duplication in the PHKD1 gene in autosomal recessive polycystic kidney disease

Jun Miyazaki, Mayuko Ito, Haruki Nishizawa, Takema Kato, Yukito Minami, Hidehito Inagaki, Tamae Oe, Masafumi Miyata, Hiroko Boda, Yuka Kiriyama, Makoto Kuroda, Takao Sekiya, Hiroki Kurahashi, Takuma Fujii

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: In the present study, we report on a couple who underwent prenatal genetic diagnosis for autosomal recessive polycystic kidney disease (ARPKD). Case presentation: 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. Conclusions: This is the first report of intragenic duplication in the PKHD1 gene in ARPKD.

Original languageEnglish
Article number98
JournalBMC Medical Genetics
Volume16
Issue number1
DOIs
Publication statusPublished - 26-10-2015

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Autosomal Recessive Polycystic Kidney
Exome
Prenatal Diagnosis
Genes
Exons
Newborn Infant
Oligohydramnios
Mutation
Amniocentesis
Multiplex Polymerase Chain Reaction
DNA Sequence Analysis
Paraffin
Microsatellite Repeats
Haplotypes
Formaldehyde
Siblings
Alleles
Kidney
Pregnancy
Lung

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

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title = "Intragenic duplication in the PHKD1 gene in autosomal recessive polycystic kidney disease",
abstract = "Background: In the present study, we report on a couple who underwent prenatal genetic diagnosis for autosomal recessive polycystic kidney disease (ARPKD). Case presentation: 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. Conclusions: This is the first report of intragenic duplication in the PKHD1 gene in ARPKD.",
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Intragenic duplication in the PHKD1 gene in autosomal recessive polycystic kidney disease. / Miyazaki, Jun; Ito, Mayuko; Nishizawa, Haruki; Kato, Takema; Minami, Yukito; Inagaki, Hidehito; Oe, Tamae; Miyata, Masafumi; Boda, Hiroko; Kiriyama, Yuka; Kuroda, Makoto; Sekiya, Takao; Kurahashi, Hiroki; Fujii, Takuma.

In: BMC Medical Genetics, Vol. 16, No. 1, 98, 26.10.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intragenic duplication in the PHKD1 gene in autosomal recessive polycystic kidney disease

AU - Miyazaki, Jun

AU - Ito, Mayuko

AU - Nishizawa, Haruki

AU - Kato, Takema

AU - Minami, Yukito

AU - Inagaki, Hidehito

AU - Oe, Tamae

AU - Miyata, Masafumi

AU - Boda, Hiroko

AU - Kiriyama, Yuka

AU - Kuroda, Makoto

AU - Sekiya, Takao

AU - Kurahashi, Hiroki

AU - Fujii, Takuma

PY - 2015/10/26

Y1 - 2015/10/26

N2 - Background: In the present study, we report on a couple who underwent prenatal genetic diagnosis for autosomal recessive polycystic kidney disease (ARPKD). Case presentation: 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. Conclusions: This is the first report of intragenic duplication in the PKHD1 gene in ARPKD.

AB - Background: In the present study, we report on a couple who underwent prenatal genetic diagnosis for autosomal recessive polycystic kidney disease (ARPKD). Case presentation: 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. Conclusions: This is the first report of intragenic duplication in the PKHD1 gene in ARPKD.

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