Phenotypic characteristics of familial glucocorticoid deficiency (FGD) type 1 and 2.
Phenotypic characteristics of familial glucocorticoid deficiency (FGD) type 1 and 2.
复制标题
DOI：
10.1111/j.1365-2265.2009.03663.x
复制
发表时间：
2010-05
影响因子：
3.2
通讯作者：
Clark AJ
中科院分区：
文献类型：
--
作者：
Chung TT;Chan LF;Metherell LA;Clark AJ
家族性糖皮质激素缺乏症（FGD）是一种罕见的常染色体隐性遗传疾病，由于编码ACTH受体[黑皮质素2受体（MC 2 R）]或其辅助蛋白[黑皮质素2受体辅助蛋白（MRAP）]的基因突变所致。这种疾病分别被称为FGD 1型和2型。本研究的目的是比较FGD 1和2之间的表型/基因型关系。纳入40例错义MC 2 R突变患者和22例MRAP突变患者。其中44名患者已被转介进行遗传筛查，18名患者由其他作者发表。FGD 1型患者就诊时的中位年龄可变，为2.0岁;范围为0.02 -16岁，这与异常高大的身材相关，平均身高SDS +1.75 ± 1.53（平均值± SD）。相比之下，FGD 2型患者的中位年龄要早得多（0.08岁;出生时至1.6岁）（P <0.01），患者的身高SDS为正常值+0.12 ± 1.35（P <0.001）。FGD 1型和2型之间的基线皮质醇或ACTH水平无差异。FGD 2型似乎出现较早。这可能反映了潜在突变的功能意义，因为所有MRAP突变都是无义或剪接位点突变，导致功能蛋白质的消除，而大多数MC 2 R突变是错义突变，并产生具有一些残留功能的蛋白质。高身材与MC 2 R突变相关，但与MRAP无关。两者之间没有其他显著的临床差异。
Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder as a result of mutation in genes encoding either the ACTH receptor [melanocortin 2 receptor (MC2R)] or its accessory protein [melanocortin 2 receptor accessory protein (MRAP)[. The disorder is known as FGD type 1 and 2, respectively. The aim of the study was to compare the phenotype/genotype relationships between FGD 1 and 2. Forty patients with missense MC2R mutations and 22 patients with MRAP mutations were included. Forty-four of these patients had been referred for genetic screening and 18 were patients published by other authors. The median age at presentation for FGD type 1 was variable at 2·0 years; range 0·02–16 years, and this was associated with unusually tall stature, mean height SDS + 1·75 ± 1·53 (mean ± SD). In contrast, FGD type 2 presented at a much earlier median age (0·08 years; range at birth to 1·6 years) (P < 0·01) and patients were of normal height SDS + 0·12 ± 1·35 (P < 0·001). No differences in baseline cortisol or ACTH levels were seen between FGD types 1 and 2. FGD type 2 appears to present earlier. This may reflect the functional significance of the underlying mutations in that all MRAP mutations are nonsense or splice site mutations that result in abolition of a functional protein, whereas most of the MC2R mutations are missense mutations and give rise to proteins with some residual function. Tall stature is associated with mutations in MC2R but not in MRAP. There were no other significant clinical distinctions between the two.
登录
查看更多内容
影响因子：
3.5
作者：
Slavotinek, AM;Hurst, JA;Wilkie, AOM
通讯作者：
Wilkie, AOM
DOI：
10.1073/pnas.0708916105
发表时间：
2007-12-18
影响因子：
11.1
作者：
Sebag, Julien A.;Hinkle, Patricia M.
通讯作者：
Hinkle, Patricia M.
DOI：
10.1001/archpedi.1959.02070010156002
发表时间：
1959-01-01
期刊：
AMA JOURNAL OF DISEASES OF CHILDREN
影响因子：
--
作者：
SHEPARD, TH;LANDING, BH;MASON, DG
通讯作者：
MASON, DG
影响因子：
--
作者：
Mazur, Artur;Koehler, Katrin;Huebner, Angela
通讯作者：
Huebner, Angela
影响因子：
3.6
作者：
MIGEON, CJ;KENNY, FM;BLIZZARD, RM
通讯作者：
BLIZZARD, RM