title: A novel mutation in the GCM2 gene causing severe congenital isolated hypoparathyroidism.
abstract: OBJECTIVE
  To investigate the GCM2 gene in three siblings with congenital hypoparathyroidism and perform functional analysis.
  
  
  METHODS
  We sequenced the GCM2 gene by PCR and analyzed the functional consequence of the mutation by transient transfection studies. Haplotype analysis was performed.
  
  
  RESULTS
  We identified a nucleotide change, c.408C>A, in exon 3 that is predicted to truncate the Gcm2 protein (p.Tyr136Ter). All three affected siblings were homozygous and both parents were heterozygous for the mutation. Transfection studies revealed the mutant mRNA but not expression of the Gcm2 protein. Haplotype analysis revealed that the two mutant GCM2 alleles shared genotypes on chromosome 6p24.2.
  
  
  CONCLUSIONS
  We describe the first GCM2 mutation in exon 3 in patients with severe congenital hypoparathyroidism. Informative genetic markers could not exclude identity by descent for the mutant alleles. Gcm2 protein was not detected after transfection, suggesting that complete lack of Gcm2 action accounts for severe hypoparathyroidism.
authors.affiliation: Division of Endocrinology, Nemours/Alfred I. duPont Hospital for Children, P.O. Box 269, Wilmington, DE 19803, USA. ddoyle@nemours.org
authors.forename: Daniel
authors.initials: D
authors.lastname: Doyle
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kirwin
authors.forename: Katia
authors.initials: K
authors.lastname: Sol-Church
authors.forename: Michael A
authors.initials: MA
authors.lastname: Levine
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D005190:Family; D005260:Female; D006801:Humans; D007011:Hypoparathyroidism / Q000151:congenital* / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C119532:GCM2 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors