title: Familial glucocorticoid deficiency type 1 due to a novel compound heterozygous MC2R mutation.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Physiotherapy, University of Rzeszów, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Mazur
authors.forename: Katrin
authors.initials: K
authors.lastname: Koehler
authors.forename: Markus
authors.initials: M
authors.lastname: Schuelke
authors.forename: Mandy
authors.initials: M
authors.lastname: Skunde
authors.forename: Mariusz
authors.initials: M
authors.lastname: Ostański
authors.forename: Angela
authors.initials: A
authors.lastname: Huebner
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000595:Amino Acid Sequence; D005260:Female; D016368:Frameshift Mutation; D005938:Glucocorticoids / Q000172:deficiency*; D006579:Heterozygote; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D043202:Steroid Metabolism, Inborn Errors / Q000188:drug therapy / Q000235:genetics*; D013972:Thyrotropin / Q000097:blood
chemical_list: D005938:Glucocorticoids; D044103:Receptor, Melanocortin, Type 2; D000324:Adrenocorticotropic Hormone; D013972:Thyrotropin; D006854:Hydrocortisone