Heterozygous p.S811F RET gene mutation associated with renal agenesis, oligomeganephronia and total colonic aganglionosis: a case report

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Background:
Several shared common gene networks participate in development of interstinal ganglia and also nephron formation; the glial cell line-derived neurotrophic factor/Ret/glial cell line-derived neurotrophic factor receptor gene network is particularly important.

Case presentation:
We encountered a patient with total colonic aganglionosis as well as right renal agenesis and oligomeganephronia. Gene analysis in this patient disclosed a heterozygous p.S811F mutation was in Ret gene exon 14, resulting in a substitution of phenylalanine for serine. The large side chain of phenylalanine obstructed the opening of the hydrophobic pocket of the Ret molecule causing interference with its interaction with adenosine triphosphate and consequent marked reduction in its enzyme activity. This could account for our patient's severe intestinal disease and renal dysplasia. We know of no previous reports of concomitant Hirschsprung’s disease and oligomeganephronia.

Conclusions:
The patient's overall illness could be considered a novel Ret gene mutation syndrome.

Keywords:
Intestine, Glial cell line-derived neurotrophic factor, RET, Kidney dysplasia, Nephron

Autoři: Keisuke Sugimoto; Tomoki Miyazawa; Hitomi Nishi; Kohei Miyazaki; Takuji Enya; Mitsuru Okada; Tsukasa Takemura ^*
Působiště autorů: Department of Pediatrics, Kindai University School of Medicine, 377-2 Ohno-higashi, Osaka-Sayama 589-8511, Japan
Vyšlo v časopise: BMC Nefrol 2016, 17:146
Kategorie: Case report
prolekare.web.journal.doi_sk: https://doi.org/10.1186/s12882-016-0354-z

© 2016 The Author(s).

Open access
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The electronic version of this article is the complete one and can be found online at: http://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-016-0354-z

Souhrn

Conclusions:
The patient's overall illness could be considered a novel Ret gene mutation syndrome.

Keywords:
Intestine, Glial cell line-derived neurotrophic factor, RET, Kidney dysplasia, Nephron

Zdroje

1. Drukker A. Oligonephropathy: from a rare childhood disorder to a possible health problem in the adult. Isr Med Assoc J. 2002;4:191–5.

2. Zaffanello M, Brugnara M, Franchini M, Fanos V. TCF2 gene mutation leads to nephro-urological defects of unequal severity: an open question. Med Sci Monit. 2008;14:78–86.

3. Salomon R, Tellier AL, Attie-Bitach T, Amiel J, Vekemans M, Lyonnet S, Dureau P, Niaudet P, Gubler MC, Broyer M. PAX2 mutations in oligomeganephronia. Kidney Int. 2001;59:457–62.

4. Marcotte M, Sharma R, Bouchard M. Gene regulatory network of renal primordium development. Pediatr Nephrol. 2014;29:637–44.

5. Demehri FR, Halaweish IF, Coran AG, Teitelbaum DH. Hirschsprungassociated enterocolitis: pathogenesis, treatment and prevention. Pediatr Surg Int. 2013;29:873–81.

6. Pini Prato A, Rossi V, Avanzini S, Mattioli G, Disma N, Jasonni V. Hirschsprung's disease: what about mortality? Pediatr Surg Int. 2011;27:473–8.

7. Wallace AS, Anderson RB. Genetic interactions and modifier genes in Hirschsprung's disease. World J Gastroenterol. 2011;7:4937–44.

8. Zhang Z, Quinlan J, Hoy W, Hughson MD, Lemire M, Hudson T, Hueber PA, Benjamin A, Roy A, Pascuet E, Goodyer M, Raju C, Houghton F, Bertram J, Goodyer P. A common RET variant is associated with reduced newborn kidney size and function. J Am Soc Nephrol. 2008;19:2027–34.

9. Knowles PP, Murray-Rust J, Kjaer S, Scott RP, Hanrahan S, Santoro M, Ibanez CF, Mcdonald NQ. Structure and chemical inhibition of the RET tyrosine kinase domain. J Biol Chem. 2006;281:33577–87.

10. Sinnassamy P, Yazbeck S, Brochu P, O’Regan S. Renal anomalies and agenesis associated with total intestinal aganglionosis. Int J Pediatr Nephrol. 1986;7:1–2.

11. Gui H, Tang WK, So MT, Proitsi P, Sham PC, Tam PK, Ngan ES, Cherny SS, Garcia-Barceló MM. RET and NRG1 interplay in Hirschsprung disease. Hum Genet. 2013;132:591–600.

12. Jeanpierre C, Macé G, Parisot M, Morinière V, Pawtowsky A, Benabou M, Martinovic J, Amiel J, Attié-Bitach T, Delezoide AL, Loget P, Blanchet P, Gaillard D, Gonzales M, Carpentier W, Nitschke P, Tores F, Heidet L, Antignac C, Salomon R. Société Française de Foetopathologie. RET and GDNF mutations are rare in fetuses with renal agenesis or other severe kidney development defects. J Med Genet. 2011;48:497–504.

13. Uesaka T, Nagashimada M, Yonemura S, Enomoto H. Diminished Ret expression compromises neuronal survival in the colon and causes intestinal aganglionosis in mice. J Clin Invest. 2008;118:1890–8.

14. So MT, Leon TY, Cheng G, Tang CS, Miao XP, Cornes BK, Diem NN, Cui L, Ngan ES, Lui VC, Wu XZ, Wang B, Wang H, Yuan ZW, Huang LM, Li L, Xia H, Zhu D, Liu J, Nguyen TL, Chan IH, Chung PH, Liu XL, Zhang R, Wong KK, Sham PC, Cherny SS, Tam PK, Garcia-Barcelo MM. RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients. PLoS One. 2011;6:e28986.

15. Fukuda N, Ichihara M, Morinaga T, Kawai K, Hayashi H, Murakumo Y, Matsuo S, Takahashi M. Identification of a novel glial cell line-derived neurotrophic factor-inducible gene required for renal branching morphogenesis. J Biol Chem. 2003;278:50386–92.