Autosomal dominant Alport syndrome due to a COL4A4 mutation with an additional ESPN variant detected by whole-exome analysis
| Autor: | Yohei Misumi, Yukimasa Kohda, Ami Hamaguchi, Yu Nagayoshi, Yuichiro Izumi, Terumasa Nakagawa, Yukio Ando, Naomichi Matsumoto, Miyuki Nakagawa, Noriko Miyake, Ken Saida, Taku Miyoshi, Rei Miura, Masashi Mukoyama, Yutaka Kakizoe |
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| Rok vydání: | 2019 |
| Předmět: |
Collagen Type IV
Pathology medicine.medical_specialty Biopsy Hearing Loss Sensorineural 030232 urology & nephrology Mutation Missense Nephritis Hereditary Case Report 030204 cardiovascular system & hematology Kidney 03 medical and health sciences Type IV collagen Young Adult 0302 clinical medicine Exome Sequencing medicine Missense mutation Humans Alport syndrome Renal Insufficiency Chronic Exome Hematuria medicine.diagnostic_test business.industry Glomerular basement membrane Microfilament Proteins General Medicine medicine.disease Pedigree medicine.anatomical_structure Mutation Sensorineural hearing loss Female Renal biopsy business Kidney disease |
| Zdroj: | CEN case reports. 9(1) |
| ISSN: | 2192-4449 |
| Popis: | 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. We report a woman in her 20 s 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 known COL4A4 (type IV collagen α4) mutation (c. 2510 G > C: p. Gly837Ala). Two pedigrees 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 this novel missense variant needs to be clarified, computational analysis predicted that the variant creates a new phosphorylation site for protein kinase C. Our case suggests a possible association of hereditary sensorineural hearing loss with ADAS. Whole-exome analysis should be considered to diagnose hereditary and multiple-organ disorders. |
| Databáze: | OpenAIRE |
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