Familial dwarfism due to a novel mutation of the growth hormone-releasing hormone receptor gene
Familial dwarfism due to a novel mutation of the growth hormone-releasing hormone receptor gene
复制标题
DOI：
10.1210/jc.84.3.917
复制
发表时间：
1999-03-01
影响因子：
5.8
通讯作者：
Levine, MA
中科院分区：
文献类型：
--
作者：
Salvatori, R;Hayashida, CY;Levine, MA
孤立性生长激素（GH）缺乏症（IGHD）是身材矮小的一种罕见原因。在印度次大陆的三个家族中，编码生长激素释放激素受体（GHRHR）的基因的相同突变已被确定为IGHD的基础。GHRHR基因缺陷的患病率和异质性尚不清楚。22个侏儒成员的一个大的，扩展的亲属至少有105个受影响的成员与常染色体隐性身材矮小进行了广泛的内分泌评估，证实显着降低或检测不到的血清GH浓度，并没有增加在不同的刺激。在索引患者中确定GHRHR基因的13个外显子和内含子-外显子边界的DNA序列。一种新的纯合5'剪接位点突变30例受试者为该突变纯合子，64例临床未受影响的患者为该突变杂合子（n = 41，包括9个专性携带者）或野生型序列纯合的（n = 23）我们描述了一种新的GHRHR基因突变，它是迄今为止所描述的家族性IGHD最大家系中侏儒症的原因。
Isolated growth hormone (GH) deficiency (IGHD) is a rare cause of short stature. The same mutation of the gene encoding the growth hormone-releasing hormone receptor (GHRHR) has been identified as the basis for IGHD in three families from the Indian subcontinent. The prevalence and heterogeneity of defects in the GHRHR gene are not known.Twenty-two dwarf members of a large, extended kindred containing at least 105 affected members with autosomal recessive short stature underwent extensive endocrine evaluation, which confirmed markedly reduced or undetectable serum concentrations of GH that did not increase in response to different stimuli. DNA sequences of the 13 exons and intron-exon boundaries of the GHRHR gene were determined in an index patient. A novel homozygous 5' splice site mutation (G-->A at position +1) in IVS1 was found. Thirty of the affected subjects tested were homozygous for this mutation, and 64 clinically unaffected patients were either heterozygous for the mutation (n = 41, including 9 obligate carriers) or homozygous for the wild-type sequence (n = 23).We describe a novel mutation in the GHRHR gene as cause of dwarfism in the largest kindred with familial IGHD described to date.