Avtor/Urednik		Hovnik, Tinka; Bratanič, Nevenka; Trebušak Podkrajšek, Katarina; Kovač, Jernej; Paro Panjan, Darja; Podnar, Tomaž; Bratina, Nataša; Battelino, Tadej
Naslov		Severe progressive obstructive cardiomyopathy and renal tubular dysfunction inDonohue syndrome with decreased insulin receptor autophosphorylation due to a novel INSR mutation
Tip		članek
Vol. in št.		Letnik 172, št. 8
Leto izdaje		2013
Obseg		str. 1125-1129
ISSN		0340-6199 - European journal of pediatrics
Jezik		eng
Abstrakt		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 patientwith 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 andinsulin receptor (IR) autophosphorylation on cultured fibroblasts were performed. A novel homozygous missense mutation p.Leu795Pro was found, locatedin the extracellular portion of the Ž subunit of the insulin receptor. The post-binding defect of the insulin receptor signaling in cultured fibroblasts demonstrated decreased insulin receptor autophosphorylation. Conclusion: 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.
Proste vsebinske oznake		insulin receptor insulin resistance mutation Donohue syndrome