A Novel Mutation in the GCM2 Gene Causing Severe Congenital Isolated Hypoparathyroidism

Overview

Journal J Pediatr Endocrinol Metab

Specialties Endocrinology
Pediatrics

Date 2012 Nov 20

PMID 23155703

Citations 8

Authors

Daniel Doyle

Susan M Kirwin

Katia Sol-Church

Michael A Levine

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Three Siblings With Familial Isolated Hypoparathyroidism: A Diagnostic Journey From to Novel Variant.

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Glial Cell Missing Homolog 2 Mutation Causing Severe Hypoparathyroidism: Report of Two Cases With Novel Mutations.

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Evolution of Our Understanding of the Hyperparathyroid Syndromes: A Historical Perspective.

Marx S, Goltzman D J Bone Miner Res. 2018; 34(1):22-37.

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Impact of intercurrent illness on calcium homeostasis in children with hypoparathyroidism: a case series.

Chinoy A, Skae M, Babiker A, Kendall D, Mughal M, Padidela R Endocr Connect. 2017; 6(8):589-594.

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Specifying the molecular pattern of sporadic parathyroid tumorigenesis-The Y282D variant of the GCM2 gene.

Marchiori E, Pelizzo M, Herten M, Townsend D, Rubello D, Merante Boschin I Biomed Pharmacother. 2017; 92:843-848.

PMID: 28609842 PMC: 6361162. DOI: 10.1016/j.biopha.2017.05.028.

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