A novel mutation in the G CM2 gene causing severe congenital isolated hypoparathyroidism

Daniel Doyle, Susan M. Kirwin, Katia Sol-Church, Michael A. Levine

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Objective: To investigate the GCM2 gene in three siblings with congenital hypoparathyroidism and perform functional analysis. Materials and 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.

Original languageEnglish (US)
Pages (from-to)741-746
Number of pages6
JournalJournal of Pediatric Endocrinology and Metabolism
Issue number7-8
StatePublished - Aug 2012
Externally publishedYes


  • GCM2
  • GCMB
  • Isolated hypoparathyroidism
  • Mutation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Pediatrics, Perinatology, and Child Health


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