Rare renal ciliopathies in non-consanguineous families that were identified by targeted resequencing

Tomohiko Yamamura, Naoya Morisada, Kandai Nozu, Shogo Minamikawa, Shingo Ishimori, Daisaku Toyoshima, Takeshi Ninchoji, Masato Yasui, Mariko Ikeda, Ichiro Morioka, Koichi Nakanishi, Hisahide Nishio, Kazumoto Iijima

Research output: Contribution to journalArticle

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Abstract

Background: Nephronophthisis-related ciliopathies (NPHP-RC) are a frequent cause of renal failure for children and adolescents. Although diagnosing these diseases clinically is difficult, a comprehensive genetic screening approach of targeted resequencing can uncover the genetic background in this complicated family of diseases. Methods: We studied three Japanese female patients with renal insufficiency from non-consanguineous parents. A renal biopsy for clinical reasons was not performed. Therefore, we did not know the diagnosis of these patients from a clinical aspect. We performed comprehensive genetic analysis using the TruSight One Sequencing Panel next generation sequencing technique. Results: We identified three different rare NPHP-RC variants in the following genes: SDCCAG8, MKKS, and WDR35. Patient 1 with SDCCAG8 homozygous deletions showed no ciliopathy-specific extrarenal manifestations, such as retinitis pigmentosa or polydactyly prior to genetic analysis. Patient 2 with a MKKS splice site homozygous mutation and a subsequent 39-amino acid deletion in the substrate-binding apical domain, had clinical symptoms of Bardet–Biedl syndrome. She and her deceased elder brother had severe renal insufficiency soon after birth. Patient 3 with a compound heterozygous WDR35 mutation had ocular coloboma and intellectual disability. Conclusions: Our results suggest that a comprehensive genetic screening system using target resequencing is useful and non-invasive for the diagnosis of patients with an unknown cause of pediatric end-stage renal disease.

Original languageEnglish
Pages (from-to)136-142
Number of pages7
JournalClinical and Experimental Nephrology
Volume21
Issue number1
DOIs
Publication statusPublished - 01-02-2017

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Kidney
Renal Insufficiency
Genetic Testing
Coloboma
Polydactyly
Mutation
Retinitis Pigmentosa
Intellectual Disability
Chronic Kidney Failure
Ciliopathies
Siblings
Parents
Parturition
Pediatrics
Biopsy
Amino Acids
Genes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Nephrology
  • Physiology (medical)

Cite this

Yamamura, T., Morisada, N., Nozu, K., Minamikawa, S., Ishimori, S., Toyoshima, D., ... Iijima, K. (2017). Rare renal ciliopathies in non-consanguineous families that were identified by targeted resequencing. Clinical and Experimental Nephrology, 21(1), 136-142. https://doi.org/10.1007/s10157-016-1256-x
Yamamura, Tomohiko ; Morisada, Naoya ; Nozu, Kandai ; Minamikawa, Shogo ; Ishimori, Shingo ; Toyoshima, Daisaku ; Ninchoji, Takeshi ; Yasui, Masato ; Ikeda, Mariko ; Morioka, Ichiro ; Nakanishi, Koichi ; Nishio, Hisahide ; Iijima, Kazumoto. / Rare renal ciliopathies in non-consanguineous families that were identified by targeted resequencing. In: Clinical and Experimental Nephrology. 2017 ; Vol. 21, No. 1. pp. 136-142.
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abstract = "Background: Nephronophthisis-related ciliopathies (NPHP-RC) are a frequent cause of renal failure for children and adolescents. Although diagnosing these diseases clinically is difficult, a comprehensive genetic screening approach of targeted resequencing can uncover the genetic background in this complicated family of diseases. Methods: We studied three Japanese female patients with renal insufficiency from non-consanguineous parents. A renal biopsy for clinical reasons was not performed. Therefore, we did not know the diagnosis of these patients from a clinical aspect. We performed comprehensive genetic analysis using the TruSight One Sequencing Panel next generation sequencing technique. Results: We identified three different rare NPHP-RC variants in the following genes: SDCCAG8, MKKS, and WDR35. Patient 1 with SDCCAG8 homozygous deletions showed no ciliopathy-specific extrarenal manifestations, such as retinitis pigmentosa or polydactyly prior to genetic analysis. Patient 2 with a MKKS splice site homozygous mutation and a subsequent 39-amino acid deletion in the substrate-binding apical domain, had clinical symptoms of Bardet–Biedl syndrome. She and her deceased elder brother had severe renal insufficiency soon after birth. Patient 3 with a compound heterozygous WDR35 mutation had ocular coloboma and intellectual disability. Conclusions: Our results suggest that a comprehensive genetic screening system using target resequencing is useful and non-invasive for the diagnosis of patients with an unknown cause of pediatric end-stage renal disease.",
author = "Tomohiko Yamamura and Naoya Morisada and Kandai Nozu and Shogo Minamikawa and Shingo Ishimori and Daisaku Toyoshima and Takeshi Ninchoji and Masato Yasui and Mariko Ikeda and Ichiro Morioka and Koichi Nakanishi and Hisahide Nishio and Kazumoto Iijima",
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Yamamura, T, Morisada, N, Nozu, K, Minamikawa, S, Ishimori, S, Toyoshima, D, Ninchoji, T, Yasui, M, Ikeda, M, Morioka, I, Nakanishi, K, Nishio, H & Iijima, K 2017, 'Rare renal ciliopathies in non-consanguineous families that were identified by targeted resequencing', Clinical and Experimental Nephrology, vol. 21, no. 1, pp. 136-142. https://doi.org/10.1007/s10157-016-1256-x

Rare renal ciliopathies in non-consanguineous families that were identified by targeted resequencing. / Yamamura, Tomohiko; Morisada, Naoya; Nozu, Kandai; Minamikawa, Shogo; Ishimori, Shingo; Toyoshima, Daisaku; Ninchoji, Takeshi; Yasui, Masato; Ikeda, Mariko; Morioka, Ichiro; Nakanishi, Koichi; Nishio, Hisahide; Iijima, Kazumoto.

In: Clinical and Experimental Nephrology, Vol. 21, No. 1, 01.02.2017, p. 136-142.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Rare renal ciliopathies in non-consanguineous families that were identified by targeted resequencing

AU - Yamamura, Tomohiko

AU - Morisada, Naoya

AU - Nozu, Kandai

AU - Minamikawa, Shogo

AU - Ishimori, Shingo

AU - Toyoshima, Daisaku

AU - Ninchoji, Takeshi

AU - Yasui, Masato

AU - Ikeda, Mariko

AU - Morioka, Ichiro

AU - Nakanishi, Koichi

AU - Nishio, Hisahide

AU - Iijima, Kazumoto

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Background: Nephronophthisis-related ciliopathies (NPHP-RC) are a frequent cause of renal failure for children and adolescents. Although diagnosing these diseases clinically is difficult, a comprehensive genetic screening approach of targeted resequencing can uncover the genetic background in this complicated family of diseases. Methods: We studied three Japanese female patients with renal insufficiency from non-consanguineous parents. A renal biopsy for clinical reasons was not performed. Therefore, we did not know the diagnosis of these patients from a clinical aspect. We performed comprehensive genetic analysis using the TruSight One Sequencing Panel next generation sequencing technique. Results: We identified three different rare NPHP-RC variants in the following genes: SDCCAG8, MKKS, and WDR35. Patient 1 with SDCCAG8 homozygous deletions showed no ciliopathy-specific extrarenal manifestations, such as retinitis pigmentosa or polydactyly prior to genetic analysis. Patient 2 with a MKKS splice site homozygous mutation and a subsequent 39-amino acid deletion in the substrate-binding apical domain, had clinical symptoms of Bardet–Biedl syndrome. She and her deceased elder brother had severe renal insufficiency soon after birth. Patient 3 with a compound heterozygous WDR35 mutation had ocular coloboma and intellectual disability. Conclusions: Our results suggest that a comprehensive genetic screening system using target resequencing is useful and non-invasive for the diagnosis of patients with an unknown cause of pediatric end-stage renal disease.

AB - Background: Nephronophthisis-related ciliopathies (NPHP-RC) are a frequent cause of renal failure for children and adolescents. Although diagnosing these diseases clinically is difficult, a comprehensive genetic screening approach of targeted resequencing can uncover the genetic background in this complicated family of diseases. Methods: We studied three Japanese female patients with renal insufficiency from non-consanguineous parents. A renal biopsy for clinical reasons was not performed. Therefore, we did not know the diagnosis of these patients from a clinical aspect. We performed comprehensive genetic analysis using the TruSight One Sequencing Panel next generation sequencing technique. Results: We identified three different rare NPHP-RC variants in the following genes: SDCCAG8, MKKS, and WDR35. Patient 1 with SDCCAG8 homozygous deletions showed no ciliopathy-specific extrarenal manifestations, such as retinitis pigmentosa or polydactyly prior to genetic analysis. Patient 2 with a MKKS splice site homozygous mutation and a subsequent 39-amino acid deletion in the substrate-binding apical domain, had clinical symptoms of Bardet–Biedl syndrome. She and her deceased elder brother had severe renal insufficiency soon after birth. Patient 3 with a compound heterozygous WDR35 mutation had ocular coloboma and intellectual disability. Conclusions: Our results suggest that a comprehensive genetic screening system using target resequencing is useful and non-invasive for the diagnosis of patients with an unknown cause of pediatric end-stage renal disease.

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