OCRL1 mutation in a boy with Dent disease, mild mental retardation, but without cataracts

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• 作者：Vladimir J. Lozanovski (1) (5)
  N. Ristoska-Bojkovska (2)
  P. Korneti (3)
  Z. Gucev (4)
  V. Tasic (2)
  
• 关键词：cataracts ; Dent disease ; Lowe syndrome ; OCRL1 ; CLCN5
• 刊名：World Journal of Pediatrics
• 出版年：2011
• 出版时间：August 2011
• 年：2011
• 卷：7
• 期：3
• 页码：280-283
• 全文大小：203KB
• 参考文献：1. Scheinman SJ, Thakker RV. X-linked nephrolithiasis/Dent鈥檚 disease and mutations in the ClC-5 chloride channel. In: Econs MJ, eds. Genetic aspects of osteoporosis and metabolic bone disease. Totowa, NJ: Humana Press, 2000: 133鈥?52. CrossRef
  2. Scheinman SJ, Pook MA, Wooding C, Pang JT, Frymoyer PA, Thakker RV. Mapping the gene causing X-linked recessive nephrolithiasis to Xp11.22 by linkage studies. J Clin Invest 1993;91:2351鈥?357. CrossRef
  3. Hoopes RR Jr, Shrimpton AE, Knohl SJ, Hueber P, Hoppe B, Matyus J, et al. Dent Disease with mutations in / OCRL1. Am J Hum Genet 2005;76:260鈥?67. CrossRef
  4. Utsch B, B枚kenkamp A, Benz MR, Besbas N, D枚tsch J, Franke I, et al. Novel / OCRL1 mutations in patients with the phenotype of Dent disease. Am J Kidney Dis 2006;48:942.e1鈥?4. CrossRef
  5. Cho HY, Lee BH, Choi HJ, Ha IS, Choi Y, Cheong HI. Renal manifestations of Dent disease and Lowe syndrome. Pediatr Nephrol 2008;23:243鈥?49. CrossRef
  6. Sekine T, Nozu K, Iyengar R, Fu XJ, Matsuo M, Tanaka R, et al. / OCRL1 mutations in patients with Dent disease phenotype in Japan. Pediatr Nephrol 2007;22:975鈥?80. CrossRef
  7. Shrimpton AE, Hoopes RR Jr, Knohl SJ, Hueber P, Reed AA, Christie PT, et al. / OCRL1 mutations in Dent 2 patients suggest a mechanism for phenotypic variability. Nephron Physiol 2009; 112:27鈥?6. CrossRef
  8. Hoopes RR Jr, Raja KM, Koich A, Hueber P, Reid R, Knohl SJ, et al. Evidence for genetic heterogeneity in Dent鈥檚 disease. Kidney Int 2004;65:1615鈥?620. CrossRef
  9. Lowe CU, Terrey M, Maclachlan EA. Organic aciduria, decreased renal ammonia production, hydrophthalmos, and mental retardation: a clinical entity. Am J Dis Child 1952;83: 164鈥?84.
  10. Gropman A, Levin S, Yao L, Lin T, Suchy S, Sabnis S, et al. Unusual renal features of Lowe syndrome in a mildly affected boy. Am J Med Genet 2000;95:461鈥?66. CrossRef
  11. R枚schinger W, Muntau AC, Rudolph G, Roscher AA, Kammerer S. Carrier assessment in families with Lowe oculocerebrorenal syndrome: novel mutations in the / OCRL1 gene and correlation of direct DNA diagnosis with ocular examination. Mol Genet Metab 2000;69:213鈥?22. CrossRef
  12. Kruger SJ, Wilson ME Jr, Hutchinson AK, Peterseim MM, Bartholomew LR, Saunders RA. Cataracts and glaucoma in patients with oculocerebrorenal syndrome. Arch Ophthalmol 2003;121:1234鈥?237. CrossRef
  13. Charnas LR, Bernardini I, Rader D, Hoeg JM, Gahl WA. Clinical and laboratory findings in the oculocerebrorenal syndrome of Lowe, with special reference to growth and renal function. N Engl J Med 1991;324:1318鈥?325. CrossRef
  14. Schramm L, Gal A, Zimmermann J, Netzer KO, Heidbreder E, Lopau K, et al. Advanced renal insufficiency in a 34-year-old man with Lowe syndrome. Am J Kidney Dis 2004;43:538鈥?43. CrossRef
  15. Tricot L, Yahiaoui Y, Teixeira L, Benabdallah L, Rothschild E, Juquel JP, et al. End-stage renal failure in Lowe syndrome. Nephrol Dial Transplant 2003;18:1923鈥?925. CrossRef
  16. Addis M, Loi M, Lepiani C, Cau M, Melis MA. / OCRL mutation analysis in Italian patients with Lowe syndrome. Hum Mutat 2004;23:524鈥?25. CrossRef
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  18. Lin T, Orrison BM, Leahey AM, Suchy SF, Bernard DJ, Lewis RA, et al. Spectrum of mutations in the / OCRL1 gene in the Lowe oculocerebrorenal syndrome. Am J Hum Genet 1997;60: 1384鈥?388. CrossRef
  19. B枚kenkamp A, B枚ckenhauer D, Cheong HI, Hoppe B, Tasic V, Unwin R, et al. Dent-2 Disease: a mild variant of Lowe syndrome. J Pediatr 2009;155:94鈥?9. CrossRef
  20. Tosetto E, Addis M, Caridi G, Meloni C, Emma F, Vergine G, et al. Locus heterogeneity of Dent鈥檚 disease: / OCRL1 and / TMEM27 genes in patients with no / CLCN5 mutations. Pediatr Nephrol 2009;24:1967鈥?973. CrossRef
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• 作者单位：Vladimir J. Lozanovski (1) (5)
  N. Ristoska-Bojkovska (2)
  P. Korneti (3)
  Z. Gucev (4)
  V. Tasic (2)
  
  1. Medical School Skopje, University Children鈥檚 Hospital, Skopje, Macedonia
  5. Universit盲tsklinik f眉r Allgemein-, Viszeral- und Transplantationschirurgie, Universit盲t Heidelberg, Im Neuenheimer Feld 132 E09, 69120, Heidelberg, Deutschland
  2. Department of Pediatric Nephrology, University Children鈥檚 Hospital, Skopje, Medical School Skopje, Skopje, Macedonia
  3. Department of Biochemistry, Medical School, Skopje, Macedonia
  4. Department of Pediatric Endocrinology and Genetics, University Children鈥檚 Hospital, Skopje, Medical School Skopje, Skopje, Macedonia
  

文摘

Background Oculocerebrorenal (Lowe) syndrome is an X-linked multisystem disease characterized by renal proximal tubulopathy, mental retardation, and congenital cataracts. We present a 19-year-old boy who was found to have low molecular weight proteinuria, hypercalciuria, mild generalized hyperaminoaciduria and intermittent microscopic hematuria at the age of 3. Methods Standard clinical and biochemical examinations and mutational analysis of the CLNC5 and OCRL1 gene were performed for the patient. Results The patient fulfilled diagnostic criteria for Dent disease, but lacked mutation in CLCN5. Sequencing of candidate genes revealed a mutation in his OCRL1 gene, which encodes for enzyme PIP2 5-phosphatase. The enzyme was not detected by western blot analysis, and decreased activity of the enzyme PIP2 5-phosphatase was observed in cultured skin fibroblasts. The boy had only mild mental retardation, mildly elevated muscle enzymes, but no neurological deficit or congenital cataracts, which are typical for Lowe syndrome. Conclusions Children with Dent phenotype who lack CLCN5 mutation should be tested for OCRL1 mutation. OCRL1 mutations may present with mild clinical features and are not necessarily associated with congenital cataracts.