Elevated Urinary Levels of 8-Hydroxy-2′-deoxyguanosine in a Japanese Child of Xeroderma Pigmentosum/Cockayne Syndrome Complex with Infantile Onset of Nephrotic Syndrome
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- Kondo Daiki
- Department of Pediatrics, Akita University Graduate School of Medicine
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- Noguchi Atsuko
- Department of Pediatrics, Akita University Graduate School of Medicine
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- Tamura Hiroaki
- Department of Pediatrics, Akita University Graduate School of Medicine
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- Tsuchida Satoko
- Devision of Pediatrics, Akita Red Cross Hospital
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- Takahashi Ikuko
- Department of Pediatrics, Akita University Graduate School of Medicine
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- Kubota Hiroki
- Department of Pediatrics, Akita University Graduate School of Medicine
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- Yano Tamami
- Department of Pediatrics, Akita University Graduate School of Medicine
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- Oyama Chikako
- Department of Pediatrics, Akita University Graduate School of Medicine
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- Sawaishi Yukio
- Devision of Pediatrics, Akita Prefectural Center on Development and Disability
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- Moriwaki Shinichi
- Department of Dermatology, Osaka Medical College
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- Takahashi Tsutomu
- Department of Pediatrics, Akita University Graduate School of Medicine
Abstract
Nucleotide excision repair (NER) is an essential biological pathway protecting against ultraviolet light-induced DNA damage. Deficient NER causes a group of rare genetic disorders including two autosomal recessive diseases, xeroderma pigmentosum (XP) and Cockayne syndrome (CS). In addition to the cutaneous photosensitivity shared in XP and CS, CS is featured by growth failure, neurological deterioration, microcephaly, and deep sunken eyes. XP/CS complex is an extremely rare type of NER disorder with a distinct phenotype that is characterized by the skin and eye pathology of XP and the somatic and neurological abnormalities of CS. Some of CS cases have been reported to be complicated with renal failure, but the genetic background or the etiology of the renal failure has not been reported. We herein report a 1-year-old Japanese boy with XP/CS complex, complicated by nephrotic syndrome. Diagnosis was confirmed by the presence of compound heterozygous mutations, G47R (c.139G>A) and R616G (c.1846C>G), in the excision repair cross-complementation group 2 (ERCC2) gene. The kidney biopsies, performed at the age of 1 year and 2 months, revealed diffuse expansion of the mesangial matrix and segmental glomerulosclerosis under light microscopy, and diffused thin capillary walls with partially lamellated regions under electron microscopy. Notably, high levels of urinary 8-hydroxy-2′-deoxyguanosin, known as an oxidative stress marker, were observed during the clinical course. The patient died at the age of 1 year and 11 months because of renal failure. We suggest the involvement of oxidative stress in the pathogenesis of nephrotic syndrome in NER disorders.
Journal
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- The Tohoku Journal of Experimental Medicine
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The Tohoku Journal of Experimental Medicine 239 (3), 231-235, 2016
Tohoku University Medical Press