Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
 
English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve
Pubget Overpricing |  
lüll
Two short children born small for gestational age with insulin-like growth factor 1 receptor haploinsufficiency illustrate the heterogeneity of its phenotype Ester WA; van Duyvenvoorde HA; de Wit CC; Broekman AJ; Ruivenkamp CA; Govaerts LC; Wit JM; Hokken-Koelega AC; Losekoot MJ Clin Endocrinol Metab 2009[Dec]; 94 (12): 4717-27CONTEXT: Small for gestational age (SGA)-born children comprise a heterogeneous group in which only few genetic causes have been identified. OBJECTIVE: To determine copy number variations in 18 growth-related genes in 100 SGA children with persistent short stature. METHODS: Copy number variations in 18 growth-related genes (SHOX, GH1, GHR, IGF1, IGF1R, IGF2, IGFBP1-6, NSD1, GRB10, STAT5B, ALS, SOCS2, and SOCS3) were determined by an "in house" multiplex ligation-dependent probe amplification kit. The deletions were further characterized by single-nucleotide polymorphism array analysis. RESULTS: Two heterozygous de novo insulin-like growth factor 1 receptor (IGF1R) deletions were found: a deletion of the complete IGF1R gene (15q26.3, exons 1-21), including distally flanking sequences, and a deletion comprising exons 3-21, extending further into the telomeric region. In one case, serum IGF-I was low (-2.78 sd score), probably because of a coexisting growth hormone (GH) deficiency. Both children increased their height during GH treatment (1 mg/m(2) per day). Functional studies in skin fibroblast cultures demonstrated similar levels of IGF1R autophosphorylation and a reduced activation of protein kinase B/Akt upon a challenge with IGF-I in comparison with controls. CONCLUSIONS: IGF1R haploinsufficiency was present in 2 of 100 short SGA children. GH therapy resulted in moderate catch-up growth in our patients. A review of the literature shows that small birth size, short stature, small head size, relatively high IGF-I levels, developmental delay, and micrognathia are the main predictors for an IGF1R deletion.|*Genetic Heterogeneity[MESH]|Adult[MESH]|Body Height/*genetics[MESH]|Child, Preschool[MESH]|Chromosome Deletion[MESH]|Chromosomes, Human, Pair 15[MESH]|Cohort Studies[MESH]|DNA/genetics[MESH]|Female[MESH]|Fibroblasts/metabolism[MESH]|Growth/genetics[MESH]|Haplotypes[MESH]|Humans[MESH]|Infant[MESH]|Infant, Newborn[MESH]|Infant, Small for Gestational Age/*growth & development[MESH]|Male[MESH]|Phenotype[MESH]|Polymorphism, Single Nucleotide[MESH]|Pregnancy[MESH]|Receptor, IGF Type 1/*deficiency/*genetics[MESH]|Signal Transduction/physiology[MESH]|Skin/cytology[MESH] |
