Hayashi Yoshitaka, Kamijo Takashi, Yamamoto Michiyo, Murata Yoshiharu, Phillips John A, Ogawa Masamichi, Seo Hisao
Department of Genetics, Division of Stress Adaptation and Protection, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Growth Horm IGF Res. 2007 Jun;17(3):249-53. doi: 10.1016/j.ghir.2007.01.019. Epub 2007 Mar 13.
To characterize the cause of a sporadic isolated growth hormone deficiency in a single patient.
Genomic DNA was extracted from blood samples of the patient and his family. Exons and exon-intron junctions of the GH-1 gene were amplified by PCR and sequenced. To characterize possible GH-1 deletions we performed Southern blot analysis and PCR-restriction fragment length analyses.
An adenine to guanine mutation at the first nucleotide of the initiation codon (Met ATGVal [GTG]) of the GH-1 gene was identified in the patient and the mother. A 7.6kb GH-1 deletion was identified in the patient, the brother and the father.
The patient was a compound heterozygote for an allele bearing a Met(-26)Val missense mutation inherited from his mother and an allele containing deletion of the entire GH-1 gene inherited from his father. The present missense mutation has not been described previously. Attention should be paid to the heterozygous gene deletion that is difficult to detect by PCR-based genetic analysis. The patient responded to GH replacement therapy fairly well, without developing anti-hGH antibody.
明确一例散发性孤立性生长激素缺乏症患者的病因。
从患者及其家族成员的血液样本中提取基因组DNA。通过聚合酶链反应（PCR）扩增生长激素-1（GH-1）基因的外显子及外显子-内含子连接区，并进行测序。为明确可能存在的GH-1基因缺失，我们进行了Southern印迹分析及PCR-限制性片段长度分析。
在患者及其母亲中，GH-1基因起始密码子（Met ATGVal [GTG]）的第一个核苷酸发生了腺嘌呤到鸟嘌呤的突变。在患者、其兄弟及父亲中均检测到一个7.6kb的GH-1基因缺失。
该患者为复合杂合子，其一个等位基因携带从母亲遗传而来的Met(-26)Val错义突变，另一个等位基因包含从父亲遗传而来的整个GH-1基因的缺失。目前该错义突变尚未见先前报道。应关注基于PCR的基因分析难以检测到的杂合子基因缺失。该患者对生长激素替代治疗反应良好，未产生抗人生长激素抗体。
