Department of Pediatrics, Sir H.N. Hospital and Research Centre, Raja Rammohan Roy Road, Mumbai, India.
Indian J Pediatr. 2012 Jul;79(7):875-83. doi: 10.1007/s12098-011-0588-5. Epub 2011 Oct 21.
To detect growth hormone GH-1 gene deletions (6.7 kb, 7.6 kb, 7 kb) in familial/nonfamilial isolated growth hormone deficiency (IGHD) and note their clinical and investigative profile.
Thirty (M16,F14) prepubertal IGHD patients aged 0.25 to 14 y, from 25 families were screened. Duration of growth failure, relevant history, clinical phenotype, and height SDS were recorded. Peak GH response to Clonidine (0.15 mg/m(2)), IGF-1, IGFBP-3 and pituitary/target gland hormones were studied. Genomic DNA of patients and family was analysed by PCR and DNA fragments were visualized on agarose gel electrophoresis.
This series was divided into deletion +ve, Group I (n=12,40%) inclusive of six familial/six nonfamilial patients, and deletion -ve Group II (n=18,60%), 5 familial/13 nonfamilial cases; in total 11/30 were familial. Onset of growth failure was earlier in Group I (p<0.001) mean 1.1 vs 4.7 y. Mean height SDS was -7 vs. -4.5 in Groups I/II (p<0.01), age at presentation 5.1 vs 8.6 y. Overhanging forehead, prominent eyes, hypoplastic facies characterized Group I with FBS <50 mg/dl in 50% and very low peak GH <0.04 vs 2.04 ng/ml (p<0.001) in Group II. In both groups IGF-1 and IGFBP3 were low, other hormones were normal and MRI showed hypoplastic adenohypophysis. 40% had GH-1 gene deletion (6.7 kb deletion in 83%, 7.6 kb and a compound heterozygote in 8% each).
In this series of 30 IGHD patients, frequency of GH-1 gene deletions (12/30) was 40%, and 54% among familial patients, and 31% with height SDS>-4. 83% had 6.7 kb deletion. Height SDS>-4, clinical phenotype, peak GH<1 ng/ml and hypoglycemia characterised IGHD Type IA.
检测家族性/非家族性孤立性生长激素缺乏症（IGHD）中生长激素 GH-1 基因缺失（6.7kb、7.6kb、7kb），并记录其临床和研究特征。
对 25 个家族的 30 名（男 16 名，女 14 名）青春期前 IGHD 患者（年龄 0.25 至 14 岁）进行筛查。记录生长发育迟缓时间、相关病史、临床表型和身高 SDS。研究了可乐定（0.15mg/m2）、IGF-1、IGFBP-3 和垂体/靶腺激素对 GH 的峰值反应。使用 PCR 分析患者和家族的基因组 DNA，并在琼脂糖凝胶电泳上观察 DNA 片段。
该系列分为阳性缺失组（Group I），包括 6 例家族性/6 例非家族性患者（n=12，占 40%）和阴性缺失组（Group II），包括 5 例家族性/13 例非家族性患者（n=18，占 60%），总共有 11/30 例为家族性。Group I 的生长发育迟缓起始年龄更早（p<0.001），均值为 1.1 岁vs 4.7 岁。Group I/II 的平均身高 SDS 分别为-7 岁和-4.5 岁（p<0.01），就诊时的年龄分别为 5.1 岁和 8.6 岁。额骨突出、眼睛突出、颜面发育不良是 Group I 的特征，50%的空腹血糖<50mg/dl，Group II 的 GH 峰值非常低，<0.04ng/ml（vs 2.04ng/ml，p<0.001）。两组 IGF-1 和 IGFBP3 均较低，其他激素均正常，MRI 显示垂体前叶发育不良。40%的患者存在 GH-1 基因缺失（83%为 6.7kb 缺失，8%为 7.6kb 和复合杂合子缺失）。
在 30 名 IGHD 患者中，GH-1 基因缺失（12/30）的频率为 40%，家族性患者中为 54%，身高 SDS>-4 的患者中为 31%。身高 SDS>-4、临床表型、GH 峰值<1ng/ml 和低血糖是 IGHD Type IA 的特征。
