THU176 Identification Of IGF1R Gene Variants In Short Children Born Small For Gestational Age

Disclosure: E. Kwon: None. M. Kang: None. I. Hwang: None. Introduction: In short stature children born small for gestational age (SGA-SS), IGF1R gene is one of important candidate genes in catch-up failure. Various deletions and single nucleotide variants of IGF1R have been reported. In this study, we aimed to find the prevalence of IGF1R gene mutation and to analyze their clinical characteristics. Method: Short stature children who met the following criteria were included: 1) Birth weight ≤ 10 percentile, and 2) Height at initial visit ≤ 3 percentile, and 3) IGF-1 SDS > 0 or Height z-score < -2.5. Calculations of IGF-1 SDS and birth weight SDS were based on previous reports (Clin chem 2012;45:16-21 and Ann Pediatr Endocrinol Metab 2014;19:146-153, respectively). Deletions were detected using SALSA MLPA probemix kit P217-B2 IGF1R (MRC Holland, Amsterdam, the Netherlands) and single nucleotide variants were analyzed by sanger sequencing of whole exon (#21) and exon-intron boundaries. Results: Mean age, birth weight SDS, height z-score, and BMI z-score of total 65 subjects were 8.0 years, -1.88, -2.83, and -0.52, respectively. Number of subjects whose birth weight ≤ 3 percentile was 25. Maximal value of IGF-1 SDS was 1.45. Family history of parental short stature (≤ 3 percentile) was found in 18 subjects. Growth hormone stimulation test was undergone in 64 subjects. Peak GH level was 1.35-41.74 ng/mL and 25 subjects had peak GH level < 10 ng/mL. A heterozygous deletion in 15q26.2q26.3 was found in one subject. She was 6.6 years old and her height z-score, BMI z-score, and birth weight SDS were -4.22, 2.36, and -3.23, respectively. She had no family history of parental short stature and her serum levels of peak GH was 3.72 ng/mL and IGF-1 SDS was -0.66. Conclusion: In this study, the prevalence of IGF1R mutation was 1.5% (1/65 subjects). Although clinical characteristics of SGA-SS subjects are various and heterogenous, IGF1-IGF1R axis is an important mechanism in SGA-SS, therefore, further investigation is needed. Presentation: Thursday, June 15, 2023