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

BMC Medical Genetics

Takuma Fujii¹  Hiroki Kurahashi⁴  Takao Sekiya¹  Makoto Kuroda⁶  Yuka Kiriyama⁶  Hiroko Boda³  Masafumi Miyata³  Tamae Ohye⁴  Hidehito Inagaki⁵  Yukito Minami¹  Takema Kato²  Haruki Nishizawa¹  Mayuko Ito¹  Jun Miyazaki¹ 

[1] Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Aichi, Japan;Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Aichi, Japan;Department of Pediatrics, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Aichi, Japan;Department of Genetic Counseling, Fujita Health University Hospital, Aichi, Japan;Genome and Transcriptome Analysis Center, Fujita Health University, Aichi, Japan;Department of Diagnostic Pathology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake 470-1192, Aichi, Japan

关键词: Duplication;    PKHD1;    Target exome;    Prenatal diagnosis;    ARPKD;   

Others  :  1230634
DOI  :  10.1186/s12881-015-0245-3

 received in 2015-01-04, accepted in 2015-10-12,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Miyazaki et al.

【 图 表 】

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