ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO796

A Case of Autosomal Dominant Alport Syndrome with a Gene Variant of ESPN, a Hearing Loss-Causative Gene, That Was Diagnosed by Whole-Exome Analysis

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Nagayoshi, Yu, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Izumi, Yuichiro, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Hamaguchi, Ami, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Miura, Rei, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Nakagawa, Terumasa, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Nakagawa, Miyuki, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Kakizoe, Yutaka, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
  • Mukoyama, Masashi, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
Introduction

Alport syndrome (AS) is a rare hereditary disease that presents with chronic kidney disease and sensorineural hearing loss and is diagnosed by its clinical features, pathological features on renal tissue, and mode of inheritance. AS has three genetic modes of heredity: X-linked, autosomal recessive, and autosomal dominant. Because the clinical and pathological features of autosomal dominant AS are much milder than those of the other two modes of heredity, definitive diagnosis is difficult.

Case Description

We report a woman in her 20s who exhibited persistent haematuria with normal renal function and sensorineural hearing loss. Her family members exhibited the same clinical findings among three generations and were suspected of having autosomal dominant AS (ADAS). Renal biopsy showed minor glomerular abnormalities on light microscopy and extensive thinning of the glomerular basement membrane on electron microscopy. Whole-exome analysis revealed a missense variant on c. 2510 G > C (p. Gly837Ala) in COL4A4 (type IV collagen α4). Two cases with the same variant have been reported previously, one as ADAS and the other as autosomal recessive AS. However, these two cases exhibited no sensorineural hearing loss. The analysis in the present case revealed another missense variant in ESPN (Espin), an actin-bundling protein, which is a causative gene for sensorineural hearing loss. Although the pathophysiological significance of such missense variant needs to be clarified, computational analysis predicted that the variant creates a new phosphorylation site for protein kinase C.

Discussion

By applying whole-exome analysis, we confirmed the diagnosis of ADAS for the present case. Our case suggests a possible association of hereditary sensorineural hearing loss with ADAS. When a suspicious hereditary disease exists, direct sequencing of the gene is usually performed. Although direct sequencing of the specific gene is crucial for diagnosis, other possible mutations may be missed. Whole-exome analysis should be considered as a method to diagnose hereditary and multiple-organ disorders.