Familial glucocorticoid deficiency type 1 due to a novel compound heterozygous MC2R mutation
Familial glucocorticoid deficiency type 1 due to a novel compound heterozygous MC2R mutation
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DOI：
10.1159/000117393
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发表时间：
2008-01-01
期刊：
影响因子：
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通讯作者：
Huebner, Angela
中科院分区：
文献类型：
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作者：
Mazur, Artur;Koehler, Katrin;Huebner, Angela
目的：描述波兰家族性糖皮质激素缺乏症患者的临床、生化和遗传特征。研究方法：详细的临床调查，激素分析和黑皮质素2受体（MC2R）基因的编码区在这个病人的测序。结果如下：我们报告一个3个月大的男孩，患有家族性糖皮质激素缺乏症，在3个月大时表现为皮肤色素沉着，肌肉无力，轻度黄疸和便秘。激素分析显示高ACTH和TSH血清浓度，低血清皮质醇浓度沿着正常的血液电解质。补充氢化可的松后，疾病症状消失，患儿完全康复。他的身体和精神发育正常。遗传分析揭示了一种新的复合杂合MC2R突变p.Leu46fs和p.Val49Met。结论：杂合的p.Leu46fs突变增加了少量的MC2R无义突变，并且是受体的第一个跨膜结构域内的第一个移码突变。根据分子建模，Val49Met突变导致第一跨膜结构域的结构变化以及跨膜结构域I和VII的潜在新型相互作用。版权所有（c）2008 S. Karger AG，巴塞尔。
Objective: Description of the clinical, biochemical and genetic features of a Polish patient with familial glucocorticoid deficiency. Methods: Detailed clinical investigation, hormonal analysis and sequencing of the coding region of the melanocortin 2 receptor (MC2R) gene in this patient. Results: 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. Conclusion: 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. Copyright (c) 2008 S. Karger AG, Basel.