PDF(Pubmed)
Abstract：
UNASSIGNED: The gonadotropin-releasing hormone receptor variant GNRHR p.Q106R (rs104893836) in homozygosity, compound heterozygosity, or single heterozygosity is often reported as the causative variant in idiopathic hypogonadotropic hypogonadism (IHH) patients with GnRH deficiency. Genotyping of a Maltese newborn cord-blood collection yielded a minor allele frequency (MAF) 10 times higher (MAF = 0.029; n = 493) than that of the global population (MAF = 0.003).
UNASSIGNED: To determine whether GNRHR p.Q106R in heterozygosity influences profiles of endogenous hormones belonging to the hypothalamic-pituitary axis and the onset of puberty and fertility in adult men (n = 739) and women (n = 239).
UNASSIGNED: Analysis of questionnaire data relating to puberty and fertility, genotyping of the GNRHR p.Q106R variant, and hormone profiling of a highly phenotyped Maltese adult cohort from the Maltese Acute Myocardial Infarction Study.
UNASSIGNED: Out of 978 adults, 43 GNRHR p.Q106R heterozygotes (26 men and 17 women) were identified. Hormone levels and fertility for all heterozygotes are within normal parameters except for TSH, which was lower in men 50 years or older.
UNASSIGNED: Hormone data and baseline fertility characteristics of GNRHR p.Q106R heterozygotes are comparable to those of homozygous wild-type individuals who have no reproductive problems. The heterozygous genotype alone does not impair the levels of investigated gonadotropins and sex steroid hormones or affect fertility. GNRHR p.Q106R heterozygotes who exhibit IHH characteristics must have at least another variant, probably in a different IHH gene, that drives pathogenicity. We also conclude that GNRHR p.Q106R is likely a founder variant due to its overrepresentation and prevalence in the island population of Malta.
UNASSIGNED: To determine whether GNRHR p.Q106R in heterozygosity influences profiles of endogenous hormones belonging to the hypothalamic-pituitary axis and the onset of puberty and fertility in adult men (n = 739) and women (n = 239).
UNASSIGNED: Analysis of questionnaire data relating to puberty and fertility, genotyping of the GNRHR p.Q106R variant, and hormone profiling of a highly phenotyped Maltese adult cohort from the Maltese Acute Myocardial Infarction Study.
UNASSIGNED: Out of 978 adults, 43 GNRHR p.Q106R heterozygotes (26 men and 17 women) were identified. Hormone levels and fertility for all heterozygotes are within normal parameters except for TSH, which was lower in men 50 years or older.
UNASSIGNED: Hormone data and baseline fertility characteristics of GNRHR p.Q106R heterozygotes are comparable to those of homozygous wild-type individuals who have no reproductive problems. The heterozygous genotype alone does not impair the levels of investigated gonadotropins and sex steroid hormones or affect fertility. GNRHR p.Q106R heterozygotes who exhibit IHH characteristics must have at least another variant, probably in a different IHH gene, that drives pathogenicity. We also conclude that GNRHR p.Q106R is likely a founder variant due to its overrepresentation and prevalence in the island population of Malta.
摘要：
■纯合性促性腺激素释放激素受体变体GNRHRp.Q106R（rs104893836），复合杂合性，或单个杂合性通常被报道为特发性低促性腺激素性性腺功能减退（IHH）患者GnRH缺乏症的致病变异。马耳他新生儿脐带血采集的基因分型产生的次要等位基因频率（MAF）比全球人群（MAF=0.003）高10倍（MAF=0.029；n=493）。
■为了确定GNRHRp.Q106R在杂合性中是否影响属于下丘脑-垂体轴的内源性激素的概况以及成年男性（n=739）和女性（n=239）的青春期和生育能力的开始。
■分析与青春期和生育有关的问卷数据，GNRHRp.Q106R变异体的基因分型，来自马耳他急性心肌梗死研究的高度表型的马耳他成人队列的激素分析。
■在978名成年人中，鉴定了43个GNRHRp.Q106R杂合子(26名男性和17名女性)。除TSH外，所有杂合子的激素水平和生育力均在正常参数范围内，这在50岁或以上的男性中更低。
■GNRHRp.Q106R杂合子的激素数据和基线生育力特征与没有生殖问题的纯合野生型个体相当。单独的杂合基因型不会损害所研究的促性腺激素和性类固醇激素的水平或影响生育能力。GNRHRp.Q106R杂合子谁表现出IHH特征必须至少有另一个变体，可能是在不同的IHH基因中，驱动致病性。我们还得出结论，GNRHRp.Q106R可能是创始人的变体，因为它在马耳他岛人口中的比例过高和普遍存在。
■为了确定GNRHRp.Q106R在杂合性中是否影响属于下丘脑-垂体轴的内源性激素的概况以及成年男性（n=739）和女性（n=239）的青春期和生育能力的开始。
■分析与青春期和生育有关的问卷数据，GNRHRp.Q106R变异体的基因分型，来自马耳他急性心肌梗死研究的高度表型的马耳他成人队列的激素分析。
■在978名成年人中，鉴定了43个GNRHRp.Q106R杂合子(26名男性和17名女性)。除TSH外，所有杂合子的激素水平和生育力均在正常参数范围内，这在50岁或以上的男性中更低。
■GNRHRp.Q106R杂合子的激素数据和基线生育力特征与没有生殖问题的纯合野生型个体相当。单独的杂合基因型不会损害所研究的促性腺激素和性类固醇激素的水平或影响生育能力。GNRHRp.Q106R杂合子谁表现出IHH特征必须至少有另一个变体，可能是在不同的IHH基因中，驱动致病性。我们还得出结论，GNRHRp.Q106R可能是创始人的变体，因为它在马耳他岛人口中的比例过高和普遍存在。
