title: Severe progressive obstructive cardiomyopathy and renal tubular dysfunction in Donohue syndrome with decreased insulin receptor autophosphorylation due to a novel INSR mutation.
abstract: Donohue syndrome (leprechaunism; OMIM *246200) is a rare, recessively inherited disorder of extreme insulin resistance due to mutations in the insulin receptor gene (INSR) causing either defects in insulin binding or receptor autophosphorylation and tyrosine kinase activity. We report a patient with pronounced clinical picture of leprechaunism who developed severe progressive hypertrophic obstructive cardiomyopathy (HOCM) and renal tubular dysfunction which improved on continuous subcutaneous infusion of recombinant human insulin-like growth factor-1 (rhIGF-I). INSR gene molecular analysis and insulin receptor (IR) autophosphorylation on cultured fibroblasts were performed. A novel homozygous missense mutation p.Leu795Pro was found, located in the extracellular portion of the β subunit of the insulin receptor. The post-binding defect of the insulin receptor signaling in cultured fibroblasts demonstrated decreased insulin receptor autophosphorylation.
  
  
  CONCLUSIONS
  Treatment with rhIGF-I partially reversed severe progressive HOCM and renal tubular dysfunction in a patient with Donohue syndrome associated with a novel p.Leu795Pro INSR gene mutation causing a severe decrease in IR autophosphorylation.
authors.affiliation: Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, Bohoričeva 20, SI-1525, Ljubljana, Slovenia.
authors.forename: Tinka
authors.initials: T
authors.lastname: Hovnik
authors.forename: Nevenka
authors.initials: N
authors.lastname: Bratanič
authors.forename: Katarina Trebušak
authors.initials: KT
authors.lastname: Podkrajšek
authors.forename: Jernej
authors.initials: J
authors.lastname: Kovač
authors.forename: Darja
authors.initials: D
authors.lastname: Paro
authors.forename: Tomaž
authors.initials: T
authors.lastname: Podnar
authors.forename: Nataša
authors.initials: N
authors.lastname: Bratina
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D056731:Donohue Syndrome / Q000235:genetics* / Q000378:metabolism; D017809:Fatal Outcome; D006130:Growth Disorders / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D036341:Intercellular Signaling Peptides and Proteins / Q000627:therapeutic use*; D020125:Mutation, Missense; D011433:Propranolol / Q000627:therapeutic use*; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C065700:myotrophin; D007334:Insulin-Like Growth Factor I; D011433:Propranolol; D011972:Receptor, Insulin