title: Familial glucocorticoid deficiency in five Arab kindreds with homozygous point mutations of the ACTH receptor (MC2R): genotype and phenotype correlations.
abstract: OBJECTIVE
  Familial glucocorticoid deficiency type 1 (FGD1) is a rare autosomal-recessive disorder resulting from defective ACTH receptor (melanocortin receptor type 2, MC2R). Individuals with this condition usually present in infancy or early childhood with the signs and symptoms of isolated glucocorticoid deficiency. To date, hypothyroidism has been reported as an associated feature in a few cases. The clinical findings along with MC2R genetic analysis of five Arab kindreds are described.
  
  
  METHODS
  The subjects were children with the clinical and biochemical features of FGD1. Three patients had associated thyroid dysfunction and two patients had associated growth hormone deficiency (GHD). Mutation analysis of MC2R was performed by direct gene sequencing.
  
  
  RESULTS
  Analysis of the MC2R gene revealed a homozygous insertion of a cytosine nucleotide between codons 153 and 154 (c.459_460insC) in all of the patients. This mutation would be expected to cause a translation frame shift after codon 154 and a premature termination codon at 248 of the MC2R mRNA (p.I154fsX248).
  
  
  CONCLUSIONS
  Associated thyroid dysfunction and GHD were clinical features in the Bedouin patients with FGD1 caused by identical homozygous frameshift mutation in the MC2R gene.
authors.affiliation: Department of Pediatrics, Farwaniya Hospital, Kuwait. hesahabeeb@yahoo.com
authors.forename: Hessa M
authors.initials: HM
authors.lastname: al Kandari
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Katsumata
authors.forename: Ibrahim
authors.initials: I
authors.lastname: al Alwan
authors.forename: Mohammed
authors.initials: M
authors.lastname: al Balwi
authors.forename: Majedah S Abdul
authors.initials: MS
authors.lastname: Rasoul
mesh_terms: D000293:Adolescent; D018912:Arabs; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004700:Endocrine System Diseases / Q000151:congenital / Q000235:genetics*; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D005938:Glucocorticoids / Q000172:deficiency*; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D017354:Point Mutation / Q000502:physiology; D018043:Receptors, Corticotropin / Q000235:genetics*
chemical_list: D005938:Glucocorticoids; D018043:Receptors, Corticotropin