Cannarella Rossella, Mattina Teresa, Condorelli Rosita A, Mongioì Laura M, Pandini Giuseppe, La Vignera Sandro, Calogero Aldo E
Department of Clinical and Experimental MedicineUniversity of Catania, Catania, Italy.
GeneticsUniversity of Catania, Catania, Italy.
Endocr Connect. 2017 Oct;6(7):528-539. doi: 10.1530/EC-17-0158.
Insulin-like growth factor 1 receptor (), mapping on the 15q26.3 chromosome, is required for normal embryonic and postnatal growth. The aim of the present study was to evaluate the gene expression and function in three unrelated patients with chromosome 15 structural abnormalities. We report two male patients with the smallest 15q26.3 chromosome duplication described so far, and a female patient with ring chromosome 15 syndrome. Patient one, with a 568 kb pure duplication, had overgrowth, developmental delay, mental and psychomotor retardation, obesity, cryptorchidism, borderline low testis volume, severe oligoasthenoteratozoospermia and gynecomastia. We found a 1.8-fold increase in the IGF1R mRNA and a 1.3-fold increase in the IGF1R protein expression ( < 0.05). Patient two, with a 650 kb impure duplication, showed overgrowth, developmental delay, mild mental retardation, precocious puberty, low testicular volume and severe oligoasthenoteratozoospermia. The IGF1R mRNA and protein expression was similar to that of the control. Patient three, with a 46,XX r(15) (p10q26.2) karyotype, displayed intrauterine growth retardation, developmental delay, mental and psychomotor retardation. We found a <0.5-fold decrease in the IGF1R mRNA expression and an undetectable IGF1R activity. After reviewing the previously 96 published cases of chromosome 15q duplication, we found that neurological disorders, congenital cardiac defects, typical facial traits and gonadal abnormalities are the prominent features in patients with chromosome 15q duplication. Interestingly, patients with 15q deletion syndrome display similar features. We speculate that both the increased and decreased gene expression may play a role in the etiology of neurological and gonadal disorders.
胰岛素样生长因子1受体（IGF1R）定位于15号染色体q26.3区域，是正常胚胎及出生后生长所必需的。本研究旨在评估3例患有15号染色体结构异常的非亲缘关系患者中IGF1R基因的表达及功能。我们报告了2例男性患者，他们携带迄今所描述的最小的15q26.3染色体重复，以及1例患有15号环状染色体综合征的女性患者。患者1有568 kb的纯合重复，表现为生长过速、发育迟缓、智力和精神运动发育迟缓、肥胖、隐睾、睾丸体积临界低值、严重少弱畸精子症和男性乳房发育。我们发现IGF1R mRNA增加了1.8倍，IGF1R蛋白表达增加了1.3倍（P<0.05）。患者2有650 kb的杂合重复，表现为生长过速、发育迟缓、轻度智力发育迟缓、性早熟、睾丸体积低和严重少弱畸精子症。IGF1R mRNA和蛋白表达与对照组相似。患者3核型为46,XX r(15)(p10q26.2)，表现为宫内生长迟缓、发育迟缓、智力和精神运动发育迟缓。我们发现IGF1R mRNA表达下降了不到0.5倍，且未检测到IGF1R活性。在回顾之前发表的96例15q染色体重复病例后，我们发现神经疾病、先天性心脏缺陷、典型面部特征和性腺异常是15q染色体重复患者的突出特征。有趣的是，15q缺失综合征患者也表现出类似特征。我们推测IGF1R基因表达的增加和减少可能在神经和性腺疾病的病因中起作用。
