Kidney Week

Abstract: FR-PO625

The Clinical Impact of Whole-Exome Sequencing by Japan’s Initiative on Rare and Undiagnosed Diseases (IRUD) Project on Renal Genetic Diseases

Session Information

• Trainee Case Reports - IV
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Trainee Case Reports

• 1002 Genetic Diseases of the Kidney: Non-Cystic

Authors

• Ishii, Akira, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan

Akira Ishii,

• Shinkawa, Kanna, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan

Kanna Shinkawa,

• Fukatsu, Atsushi, Fukatsu Medical Clinic, Anjo, Japan

Atsushi Fukatsu,

• Nakagawa, Naoko, Department of Medical Ethics/Medical Genetics, Kyoto University School of Public Health, Kyoto, Japan

Naoko Nakagawa,

• Wada, Takahito, Department of Medical Ethics/Medical Genetics, Kyoto University School of Public Health, Kyoto, Japan

Takahito Wada,

• Kondo, Naoya, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan

Naoya Kondo,

• Sakai, Kaoru, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan

Kaoru Sakai,

• Endo, Shuichiro, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan

Shuichiro Endo,

• Yokoi, Hideki, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan

Hideki Yokoi,

• Matsubara, Takeshi, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan

Takeshi Matsubara,

• Kosugi, Shinji, Department of Medical Ethics/Medical Genetics, Kyoto University School of Public Health, Kyoto, Japan

Shinji Kosugi,

• Kosaki, Kenjiro, Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan

Kenjiro Kosaki,

• Yanagita, Motoko, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan

Motoko Yanagita,

Introduction

There exist many patients who are suffering from rare, undiagnosed kidney diseases. In 2015, the Japan Agency for Medical Research and Development (AMED) launched the Initiative on Rare and Undiagnosed Diseases (IRUD). IRUD is a national project to analyze whole-exome sequence by using next-generation sequencer.

Case Description

Case 1: A 30-year-old woman, who was diagnosed with Retinitis Pigmentosa, developed renal dysfunction (serum creatinine level, 4.8 mg/dl). She had hypokalemia and metabolic acidosis, and her 31-year-old brother also had same symptoms and was receiving hemodialysis. Her brother was suspected of having Nephronophthisis and the genetic examination was performed but could not find the NPHP gene mutation. Therefore, we examined exome sequencing by IRUD. By genetic analysis, she had compound heterozygous missense variants in ALMS1 gene c.[4331A>T];[7973C>G] which were also found in her brother, but it seemed atypical presentations as Alstrom syndrome because they did not show neither obesity nor type 2 diabetes.
Case 2: A 57-year-old man, who was diagnosed with hematuria 37 years ago, developed proteinuria and renal dysfunction (serum creatinine level, 3.5 mg/dl). Her mother and younger sister also had hematuria and proteinuria and his three sons also had hematuria. From his family history of renal disease including women, Alport syndrome which is probably due to COL4A3 or COL4A4 mutation was suspected. Exome sequencing found deletion and missense variants in COL4A4 gene c.[1323_1340del]; [2045A>G] in the patient. These mutations had not been reported so far as responsible genes in Alport syndrome.

Discussion

These genetic mutations found in the two cases were predicted to cause the phenotypes of diseases. Whole-exome sequencing by IRUD is a powerful tool for diagnosis of rare and atypical renal genetic diseases. Sharing and accumulating the genetic data of diseases will be important for further elucidation of the pathology.