title: Novel heterozygous IGF1R mutation in two brothers with developing impaired glucose tolerance.
abstract: Infants born small for gestational age (SGA) are at risk to develop metabolic complications. Insulin-like growth factor 1 (IGF-1) resistance due to IGF-1 receptor (IGF1R) mutations is a rare genetic condition that causes proportionate growth retardation. The contribution of an impaired IGF1R function to the development of comorbidities such as disturbed glucose homeostasis is not well understood. Genetic analysis and detailed auxological, endocrine and psychological investigations in two male SGA siblings were performed. The two patients and their father bear a novel heterozygous mutation (p.Cys1248Tyr) in the IGF1R gene. Both brothers displayed very similar growth pattern before and during recombinant human growth hormone treatment, whereas oral glucose tolerance tests showed variable manifestations of progressive impaired glucose tolerance. The father had already developed type 2 diabetes mellitus. Growth retardation in our patients is likely caused by the IGF1R mutation that might predispose to disturbances of carbohydrate homeostasis. Therefore, a close metabolic monitoring of affected patients is indicated, particularly if growth hormone therapy is commenced.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Burkhardt
authors.forename: Julia
authors.initials: J
authors.lastname: Gesing
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kapellen
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kratzsch
authors.forename: Marina
authors.initials: M
authors.lastname: Schlicke
authors.forename: Heike
authors.initials: H
authors.lastname: Stobbe
authors.forename: Anke
authors.initials: A
authors.lastname: Tönjes
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klammt
authors.forename: Roland
authors.initials: R
authors.lastname: Pfäffle
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D018149:Glucose Intolerance / Q000150:complications / Q000235:genetics*; D006130:Growth Disorders / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics*; D035781:Siblings
chemical_list: C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; D017526:Receptor, IGF Type 1