Mazur Artur, Koehler Katrin, Schuelke Markus, Skunde Mandy, Ostański Mariusz, Huebner Angela
Institute of Physiotherapy, University of Rzeszów, Poland.
Horm Res. 2008;69(6):363-8. doi: 10.1159/000117393. Epub 2008 Mar 17.
Description of the clinical, biochemical and genetic features of a Polish patient with familial glucocorticoid deficiency.
Detailed clinical investigation, hormonal analysis and sequencing of the coding region of the melanocortin 2 receptor (MC2R) gene in this patient.
We report on a 3-month-old boy with familial glucocorticoid deficiency who presented at the age of 3 months with skin hyperpigmentation, muscle weakness, mild jaundice and constipation. Hormonal analyses revealed high ACTH and TSH serum concentrations, low serum cortisol concentration along with normal blood electrolytes. On hydrocortisone supplementation, the disease symptoms disappeared and the child recovered completely. His physical and mental development progresses normally. Genetic analysis disclosed a novel compound heterozygous MC2R mutation p.Leu46fs and p.Val49Met.
The heterozygous p.Leu46fs mutation adds to the small number of MC2R nonsense mutations and is the first frameshift mutation within the first transmembrane domain of the receptor. According to molecular modeling the Val49Met mutation results in a structural change of the first transmembrane domain and in a potential novel interaction of the transmembrane domains I and VII.
描述一名患有家族性糖皮质激素缺乏症的波兰患者的临床、生化和遗传特征。
对该患者进行详细的临床调查、激素分析以及黑皮质素2受体（MC2R）基因编码区测序。
我们报告了一名3个月大患有家族性糖皮质激素缺乏症的男孩，他在3个月大时出现皮肤色素沉着、肌肉无力、轻度黄疸和便秘。激素分析显示血清促肾上腺皮质激素（ACTH）和促甲状腺激素（TSH）浓度升高，血清皮质醇浓度降低，而血液电解质正常。补充氢化可的松后，疾病症状消失，患儿完全康复。其身体和智力发育正常进展。基因分析发现了一种新的复合杂合MC2R突变p.Leu46fs和p.Val49Met。
杂合p.Leu46fs突变增加了MC2R无义突变的数量，并且是该受体第一个跨膜结构域内的首个移码突变。根据分子模型，Val49Met突变导致第一个跨膜结构域的结构变化以及跨膜结构域I和VII之间潜在的新相互作用。
