title: Novel compound heterozygous mutation of the MC2R gene in a patient with familial glucocorticoid deficiency.
abstract: Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder characterised by glucocorticoid insufficiency without mineralocorticoid deficiency. Here, we report a 2 year-old girl with FGD, showing tall stature and skin pigmentation, but no abnormalities of the external genitalia. Serum sodium, potassium and chloride levels were within normal ranges. Endocrinological analysis revealed low serum cortisol (<5.5 nmol/1), elevated plasma ACTH (875.2 pmol/1) and low 17alpha-hydroxyprogesterone (< 0.303 nmol/l). We suspected the patient of having FGD type 1. Direct and allele-specific sequence analyses of the melanocortin 2 receptor gene (MC2R) revealed compound heterozygous mutations (C21Y and R146H) in the MC2R gene. Her father and mother each had heterozygous C21Y and R146H mutations, respectively, without symptoms of glucocorticoid deficiency. This is the first report of FGD associated with a compound heterozygous mutation of C21Y and R146H in the MC2R gene.
authors.affiliation: Department of Paediatrics, Shinshu University School ofMedicine, Matsumoto, Japan. matsuura@hsp.md.shinshu-u.ac.jp
authors.forename: Hiroki
authors.initials: H
authors.lastname: Matsuura
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shiohara
authors.forename: Mizuki
authors.initials: M
authors.lastname: Yamano
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurata
authors.forename: Fumi
authors.initials: F
authors.lastname: Arai
authors.forename: Kenichi
authors.initials: K
authors.lastname: Koike
mesh_terms: D000483:Alleles; D002675:Child, Preschool; D003001:Cloning, Molecular; D005260:Female; D005938:Glucocorticoids / Q000172:deficiency* / Q000627:therapeutic use; D006128:Growth / Q000235:genetics / Q000502:physiology; D006579:Heterozygote; D020249:Hormone Replacement Therapy; D006801:Humans; D009154:Mutation / Q000502:physiology*; D010859:Pigmentation Disorders / Q000235:genetics; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics*; D043202:Steroid Metabolism, Inborn Errors / Q000235:genetics*
chemical_list: D005938:Glucocorticoids; D044103:Receptor, Melanocortin, Type 2