Abstract
Haploinsufficiency of the gene encoding the insulin-like growth factor 1 receptor (IGF1R), either caused by telomeric 15q26 deletions, or by heterozygous point mutations in IGF1R, segregate with short stature and various other phenotypes, including microcephaly and dysmorphic facial features. Psychomotor retardation and behavioral anomalies have been seen in some cases. Here we report small, intragenic deletions of IGF1R, identified by chromosome microarray analysis in two unrelated families affected primarily with neuropsychiatric phenotypes including developmental delay, intellectual disability and aggressive/autoaggressive behaviors. The deletions are in frame, and both wild-type and mutant mRNAs are expressed as measured by quantitative real-time PCR. While short stature is considered a phenotypic hallmark of IGF1R haploinsufficiency, the present report suggests that in frame exon deletions of IGF1R present predominantly with cognitive and neuropsychiatric phenotypes.
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Acknowledgements
We thank the patients and parents for their willingness to participate in our research study. Dr Schaaf ’s work is generously supported by the Joan and Stanford Alexander family, the Doris Duke Charitable Foundation, and the Ting Tsung and Wei Fong Chao Foundation. Dr Witsch’s work was supported by the Felgenhauer Foundation of the German Neurological Society. We thank Mrs Jessica Tao for excellent technical assistance.
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Drs Schaaf, Stankiewicz and Cheung are faculty members of the Department of Molecular and Human Genetics at Baylor College of Medicine, which derives revenue from the chromosomal microarray analysis offered in the Medical Genetics Laboratory. The remaining authors declare no conflict of interest.
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Witsch, J., Szafranski, P., Chen, CA. et al. Intragenic deletions of the IGF1 receptor gene in five individuals with psychiatric phenotypes and developmental delay. Eur J Hum Genet 21, 1304–1307 (2013). https://doi.org/10.1038/ejhg.2013.42
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DOI: https://doi.org/10.1038/ejhg.2013.42
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