Here we report ABL1 germline variants cosegregating with an autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities, and failure to thrive.
Biotin and pantothenic acid oversupplementation to conditional SLC5A6 KO mice prevents the development of intestinal mucosal abnormalities and growth defects.
The identification of a second case of severe growth failure associated with STAT5b mutation implicates a unique and critical role for STAT5b in GH stimulation of IGF-I gene expression and statural growth.
Our results suggest that there is minimal DNA sequence variability in the human IGF-I gene and that mutations in IGF-I exons are infrequent causes of growth failure.
The results of the in-vitro study do not support the hypothesis that IGF-I/IGF-II resistance is a major pathogenetic mechanism responsible for the growth failure in the subgroup of SRS children with IGF2/H19 hypomethylation.
Categorization of the causes for ISS by insulin-like growth factor I (IGF-I) concentrations provides a basis for speculation about the potential for IGF-I gene polymorphisms or binding protein abnormalities influencing the development of ISS-related growth failure.
Individuals with a deletion of 15q26.1-->qter which contains the insulin-like growth factor-I (IGF-I) receptor gene exhibit phenotypical similarities to patients with Silver-Russell syndrome (SRS) who represent a group of short children affected by pre- and postnatal growth failure and several dysmorphic features.
Mutations in the pregnancy-associated plasma protein A2 (PAPP-A2) gene have recently been shown to cause postnatal growth failure in two prepubertal patients from a non-consanguineous Spanish family due to the resulting decrease in IGF1 bioavailability.
Patients with single allele defects in the gene encoding the type 1 IGF receptor have been reported to have growth failure, but fibroblasts from affected patients have not exhibited insensitivity to the effects of IGF-I in vitro.
During follow-up he manifested complications from the hydrocephalus and NDI including global developmental delay and growth failure with low IGF-1 and hypothyroidism.
The spectrum of associated anomalies in this newly recognised phenotype complex consists of growth failure, typical facial anomalies with additional (previously unreported) nervous system abnormalities (e.g. sensorineural deafness) and somatomedin C deficiency.