title: Heterozygous p.S811F RET gene mutation associated with renal agenesis, oligomeganephronia and total colonic aganglionosis: a case report.
abstract: 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.
  
  
  
  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.
  
  
  
  The patient's overall illness could be considered a novel Ret gene mutation syndrome.
authors.affiliation: Department of Pediatrics, Kindai University School of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, 589-8511, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: Department of Pediatrics, Kindai University School of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, 589-8511, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Miyazawa
authors.affiliation: Department of Pediatrics, Kindai University School of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, 589-8511, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nishi
authors.affiliation: Department of Pediatrics, Kindai University School of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, 589-8511, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Miyazaki
authors.affiliation: Department of Pediatrics, Kindai University School of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, 589-8511, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Enya
authors.affiliation: Department of Pediatrics, Kindai University School of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, 589-8511, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Pediatrics, Kindai University School of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, 589-8511, Japan. tsukasa@med.kindai.ac.jp.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Takemura
mesh_terms: D002648:Child; D000013:Congenital Abnormalities / Q000000981:diagnostic imaging* / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006627:Hirschsprung Disease / Q000000981:diagnostic imaging* / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000002:abnormalities* / Q000000981:diagnostic imaging; D007674:Kidney Diseases / Q000151:congenital* / Q000000981:diagnostic imaging / Q000235:genetics; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051096:Proto-Oncogene Proteins c-ret / Q000737:chemistry / Q000235:genetics*
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: Glial cell line-derived neurotrophic factor; Intestine; Kidney dysplasia; Nephron; RET