Abstract
Insulin-like growth factor receptor (IGF-1R) deficiency is a rare form of short stature, and is difficult to clinically diagnose. Targeted next-generation sequencing (NGS) allows for the rapid and inexpensive assessment of short stature. We identified mutations in the pedigree of a Chinese boy with severe short stature using targeted NGS; we then assessed the clinical characteristics and evaluated the efficacy of growth hormone therapy. NGS analysis revealed a novel heterozygous missense mutation in exon3 (\(\hbox {c.926C}{>}\hbox {T}\), p.S309L) of the type-I IGF-1R gene in the proband, which was inherited from the mother. The proband, mother and grandfather suffered from severe growth failure. After recombinant human growth hormone therapy, the patient’s growth rate increased. The novel missense mutation in IGF-1R (\(\hbox {c.926C}>\hbox {T}\), p.S309L) is associated with severe short stature in Chinese individuals. Targeted NGS may enable efficient diagnosis and genetic consultation of children with short stature.
References
Essakow J. L., Lauterpacht A., Lilos P., Kauli R. and Laron Z. 2016 Genetic mutations, birth lengths, weights and head circumferences of children with IGF-I receptor defects. Comparison with other congenital defects in the GH/IGF-I axis. Pediatr. Endocrinol. Rev. 14, 19–26.
Fujimoto M., Kawashima Sonoyama Y., Hamajima N., Hamajima T., Kumura Y., Miyahara N. et al. 2015 Heterozygous nonsense mutations near the C-terminal region of IGF1R in two patients with small-for-gestational-age-related short stature. Clin. Endocrinol. (Oxf) 83, 834–841.
Juanes M., Guercio G., Marino R., Berensztein E., Warman D. M., Ciaccio M. et al. 2015 Three novel IGF1R mutations in microcephalic patients with prenatal and postnatal growth impairment. Clin. Endocrinol. (Oxf) 82, 704–711.
Kawashima Y., Hakuno F., Okada S., Hotsubo T., Kinoshita T., Fujimoto M. et al. 2014 Familial short stature is associated with a novel dominant-negative heterozygous insulin-like growth factor 1 receptor (IGF1R) mutation. Clin. Endocrinol. (Oxf) 81, 312–314.
Klammt J., Kiess W. and Pfaffle R. 2011 IGF1R mutations as cause of SGA. Best Pract. Res. Clin. Endocrinol. Metab. 25, 191–206.
Mahmoud R., Naidu A., Risheg H. and Kimonis V. 2017 Response to growth hormone treatment in a patient with insulin-like growth factor 1 receptor (IGF1R) deletion. J. Clin. Res. Pediatr. Endocrinol. 9, 380–386.
Muller E., Dunstheimer D., Klammt J., Friebe D., Kiess W., Kratzsch J. et al. 2012 Clinical and functional characterization of a patient carrying a compound heterozygous pericentrin mutation and a heterozygous IGF1 receptor mutation. PLoS One 7, e38220.
Ocaranza P., Golekoh M. C., Andrew S. F., Guo M. H., Kaplowitz P., Saal H. et al. 2017 Expanding Genetic and Functional Diagnoses of IGF1R Haploinsufficiencies. Horm. Res. Paediatr. 87, 412–422.
Simon D., Leger J. and Carel J. C. 2008 Optimal use of growth hormone therapy for maximizing adult height in children born small for gestational age. Best Pract. Res. Clin. Endocrinol. Metab. 22, 525–537.
Yang Y., Huang H., Wang W., Yang L., Xie L. L. and Huang W. 2013 Association of insulin growth factor-1 receptor gene polymorphisms with genetic susceptibility to idiopathic short stature. Genet. Mol. Res. 12, 4768–4779.
Acknowledgements
This work was supported in part by the National Key Research and Development Program of China (2016YFC1305301) and the National Natural Science Foundation of China (No. 81460501).
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Corresponding editor: H. A. Ranganath.
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Yang, Y., Huang, H., Chen, K. et al. Novel mutation of type-1 insulin-like growth factor receptor (IGF-1R) gene in a severe short stature pedigree identified by targeted next-generation sequencing. J Genet 98, 16 (2019). https://doi.org/10.1007/s12041-019-1067-4
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DOI: https://doi.org/10.1007/s12041-019-1067-4