Pelosi Paola, Lapi Elisabetta, Cavalli Loredana, Verrotti Alberto, Pantaleo Marilena, de Martino Maurizio, Stagi Stefano
Department of Health Sciences, University of Florence, Anna Meyer Children's University Hospital, Florence, Italy.
Genetics and Molecular Medicine Unit, Anna Meyer Children's University Hospital, Florence, Italy.
Front Endocrinol (Lausanne). 2017 Sep 5;8:227. doi: 10.3389/fendo.2017.00227. eCollection 2017.
Haploinsufficiency of the insulin-like growth factor ()-1 receptor () gene is a rare, probably under-diagnosed, cause of short stature. However, the effects of haploinsufficiency on glucose metabolism, bone status, and metabolism have rarely been investigated. We report the case of a patient referred to our center at the age of 18 months for short stature, failure to thrive, and Silver-Russell-like phenotype. Genetic analysis did not show hypomethylation of the 11p15.5 region or uniparental disomy of chromosome 7. Growth hormone (GH) stimulation tests revealed GH deficiency, whereas IGF-1 was 248 ng/mL. r-hGH treatment showed only a slight improvement (from -4.4 to -3.5 SDS). At 10 years of age, the child was re-evaluated: CGH-array identified a heterozygous 4.92 Mb deletion in 15q26.2, including the gene. Dual-energy X-ray absorptiometry showed a normal bone mineral density -score, while peripheral quantitative computed tomography revealed reduced cortical and increased trabecular elements. A phalangeal bone quantitative ultrasonography showed significantly reduced amplitude-dependent speed of sound and bone transmission time values. The changes in bone architecture, quality, and metabolism in heterozygous IGF1R deletion patients, support the hypothesis that IGF-1 can be a key factor in bone modeling and accrual.
胰岛素样生长因子（IGF）-1受体（IGF1R）基因单倍剂量不足是身材矮小的一种罕见病因，可能存在诊断不足的情况。然而，IGF1R单倍剂量不足对糖代谢、骨骼状态及代谢的影响鲜有研究。我们报告了一例18个月大因身材矮小、生长发育迟缓及类似Silver-Russell综合征表型转诊至我院的患者。基因分析未显示11p15.5区域低甲基化或7号染色体单亲二倍体。生长激素（GH）刺激试验显示生长激素缺乏，而IGF-1为248 ng/mL。重组人生长激素（r-hGH）治疗仅略有改善（从-4.4 SDS至-3.5 SDS）。患儿10岁时进行了重新评估：比较基因组杂交阵列（CGH-array）鉴定出15q26.2区域存在一个4.92 Mb的杂合缺失，包含IGF1R基因。双能X线吸收法显示骨密度Z值正常，而外周定量计算机断层扫描显示皮质骨减少、小梁骨增加。指骨定量超声检查显示振幅依赖的声速和骨传导时间值显著降低。杂合性IGF1R缺失患者骨骼结构、质量和代谢的变化支持了IGF-1可能是骨骼建模和骨量积累关键因素的假说。
