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

• Published in: Clinical and experimental nephrology 2017-02, Vol.21 (1), p.136-142
• Main Authors: Yamamura, Tomohiko, Morisada, Naoya, Nozu, Kandai, Minamikawa, Shogo, Ishimori, Shingo, Toyoshima, Daisaku, Ninchoji, Takeshi, Yasui, Masato, Taniguchi-Ikeda, Mariko, Morioka, Ichiro, Nakanishi, Koichi, Nishio, Hisahide, Iijima, Kazumoto
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Autoantigens - genetics; Child, Preschool; Ciliopathies - diagnosis; Ciliopathies - genetics; Consanguinity; Disease Progression; DNA Mutational Analysis; Female; Genetic Markers; Genetic Predisposition to Disease; Genetic Testing - methods; Group II Chaperonins - genetics; Heterozygote; High-Throughput Nucleotide Sequencing; Homozygote; Humans; Kidney Diseases - diagnosis; Kidney Diseases - genetics; Kidney Failure, Chronic - diagnosis; Kidney Failure, Chronic - genetics; Magnetic Resonance Imaging; Medicine; Medicine & Public Health; Neoplasm Proteins - genetics; Nephrology; Original Article; Phenotype; Predictive Value of Tests; Proteins - genetics; Sequence Deletion; Urology
• ISSN: 1342-1751; 1437-7799
• DOI: 10.1007/s10157-016-1256-x

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.