单纯性生长激素缺乏症I_A型患者GH_1基因缺失位点的研究

DETECTION OF GROWTH HORMONE GENE DELETION SITE IN TWO CHINESE ISOLATED GROWTH HORMONE DEFICIENCY TYPE Ⅰ A PATIENTS

单纯性生长激素缺乏症（ＩＧＨＤⅠＡ型）的分子基础是生长激素结构基因（ＧＨ１）的缺失。为了进一步明确ＧＨ１基因缺失的发生机理，应用ＰＣＲ方法钓出了２名患者的包括缺失位点在内的基因片段，克隆后用双脱氧法进行序列分析。结果发现：２例患者在ＧＨ基因簇１８３３～２４２９ｂｐ、８４４６～９０４２ｂｐ位点的两段５９６ｂｐ（９９％同源）基因片段间发生了３次基因的同源性重组交换，从而导致了包括ＧＨ１基因在内的６．７ｋｂ的基因片段缺失。为研究同源重组的分子机理提供了依据。

Isolated growth hormone deficiency type Ⅰ A (IGHD Ⅰ A) is an autosomal recessive disease caused by deletion of both growth hormone 1 alleles (GH 1). The fragments of two Chinese IGHD Ⅰ A patients including the breakpoint were obtained with PCR technique. DNA sequence analysis showed that three crossovers occurred within two 99% homologous, 596 base pair(bp) segments that flanked GH 1 alleles. It resulted in 6.7 kb of DNA segment containing growth hormone gene deletion.These results suggest that homolgous recombination is dependent on the length and degree of sequence homology.