Majewska Katarzyna Anna, Kedzia Andrzej, Kontowicz Przemyslaw, Prauzinska Magdalena, Szydlowski Jaroslaw, Switonski Marek, Nowacka-Woszuk Joanna
Department of Clinical Auxology and Pediatric Nursing, Poznan University of Medical Sciences, Szpitalna 27/33, Poznan, Poland.
Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Wolynska 33, 60-637, Poznan, Poland.
Endocrine. 2020 Jul;69(1):157-164. doi: 10.1007/s12020-020-02305-5. Epub 2020 Apr 27.
Short stature in children is a significant medical problem which, without proper diagnosis and treatment, can lead to long-term consequences for physical and psychological health in adult life. Since human height is a polygenic and highly heritable trait, numerous variants in the genes involved in growth-including the growth hormone (GH1) gene-have been identified as causes of short stature.
In this study, we performed for the first time molecular analysis of the GH1 gene in a cohort (n = 186) of Polish children and adolescents with short stature, suffering from growth hormone deficiency (GHD) or idiopathic short stature (ISS), and a control cohort (n = 178).
Thirteen SNP variants were identified, including four missense variants, six in 5'UTR, and three in introns. The frequency of minor missense variants was low (<0.02) and similar in the compared cohorts. However, two of these variants, Ala39Val (rs151263636) and Arg42Leu (rs371953554), were found (heterozygote status) in only two GHD patients. These substitutions, according to databases, can potentially be deleterious.
Mutations of GH1 causing short stature are very rare in the Polish population, but two potentially causative variants need further studies in a larger cohort of GHD patients.
儿童身材矮小是一个重大的医学问题，若未经适当诊断和治疗，可能会对成年后的身心健康造成长期影响。由于人类身高是一种多基因且高度可遗传的性状，已确定参与生长的基因（包括生长激素（GH1）基因）中的众多变异是身材矮小的原因。
在本研究中，我们首次对一组波兰身材矮小的儿童和青少年（n = 186）进行了GH1基因的分子分析，这些儿童和青少年患有生长激素缺乏症（GHD）或特发性身材矮小（ISS），并设置了一个对照组（n = 178）。
共鉴定出13个单核苷酸多态性（SNP）变异，包括4个错义变异、6个位于5'非翻译区（UTR）的变异和3个内含子变异。次要错义变异的频率较低（<0.02），在比较的队列中相似。然而，其中两个变异，即Ala39Val（rs151263636）和Arg42Leu（rs371953554），仅在两名GHD患者中被发现（杂合子状态）。根据数据库，这些替换可能具有潜在的有害性。
在波兰人群中，导致身材矮小的GH1基因突变非常罕见，但两个潜在的致病变异需要在更大规模的GHD患者队列中进一步研究。
