Woods K A, Camacho-Hübner C, Barter D, Clark A J, Savage M O
University Department of Paediatrics, John Radcliffe Hospital, Oxford, UK.
Acta Paediatr Suppl. 1997 Nov;423:39-45. doi: 10.1111/j.1651-2227.1997.tb18367.x.
The first human case of a homozygous molecular defect in the gene encoding insulin-like growth factor I (IGF-I) is described. The patient was a 15-year-old boy from a consanguineous pedigree who presented with severe intrauterine growth failure, sensorineural deafness and mild mental retardation. Endocrine evaluation of the growth hormone (GH)--IGF-I axis revealed elevated GH secretion, undetectable serum IGF-I and normal serum IGF-binding protein-3, acid-labile subunit, and GH-binding activity. Analysis of the IGF-I gene revealed a homozygous partial IGF-I gene deletion involving exons 4 and 5, which encodes a severely truncated mature IGF-I peptide. This patient demonstrates that complete disruption of the IGF-I gene in man is compatible with life, and indicates a major role for IGF-I in human fetal growth. In addition, his neurological abnormalities suggest that IGF-I may be involved in central nervous system development.
本文描述了首例编码胰岛素样生长因子I（IGF-I）基因纯合分子缺陷的人类病例。该患者是一名来自近亲家系的15岁男孩，表现为严重的宫内生长迟缓、感音神经性耳聋和轻度智力发育迟缓。对生长激素（GH）-IGF-I轴的内分泌评估显示GH分泌升高、血清IGF-I检测不到，而血清IGF结合蛋白-3、酸性不稳定亚基和GH结合活性正常。对IGF-I基因的分析显示，存在一个涉及外显子4和5的纯合部分IGF-I基因缺失，该缺失编码一个严重截短的成熟IGF-I肽。该患者表明，人类IGF-I基因的完全破坏与生命相容，并提示IGF-I在人类胎儿生长中起主要作用。此外，他的神经学异常表明IGF-I可能参与中枢神经系统发育。
