J Korean Med Sci.  2013 Oct;28(10):1489-1495. 10.3346/jkms.2013.28.10.1489.

Genetic and Clinical Characteristics of Korean Patients with Isolated Hypoparathyroidism: From the Korean Hypopara Registry Study

• Park SY
• Eom YS
• Choi B
• Yi HS
• Yu SH
• Lee K
• Jin HS
• Chung YS
• Jung TS
• Lee S

• KMID: 1777686
• DOI: http://doi.org/10.3346/jkms.2013.28.10.1489

Abstract

Isolated hypoparathyroidism (IH) shows heterogeneous phenotypes and can be caused by defects in a variety of genes. The goal of our study was to determine the clinical features and to analyze gene mutations in a large cohort of Korean patients with sporadic or familial IH. We recruited 23 patients. They showed a broad range of onset age and various values of biochemical data. Whole exome sequencing was performed on two affected cases and one unaffected individual in a family. All coding exons and exon-intron borders of GCMB, CASR, and prepro-PTH were sequenced using PCR-amplified DNA. In one family who underwent the whole exome sequencing analysis, approximately 300 single nucleotide changes emerged as candidates for genetic alteration. Among them, we identified a functional mutation in exon 2 of GCMB (C106R) in two affected cases. Besides, heterozygous gain-of-function mutations in the CASR gene were found in other subjects; D410E and P221L. We also found one single nucleotide polymorphism (SNP) in the prepro-PTH gene, five SNPs in the CASR gene, and four SNPs in the GCMB gene. The current study represents a variety of biochemical phenotypes in IH patients with the molecular genetic diagnosis of IH.

Keyword

CASR; GCMB; Hypocalcemia; Hypoparathyroidism; Prepro-PTH

MeSH Terms

Adult
Aged
Asian Continental Ancestry Group/*genetics
Cohort Studies
Heterozygote
Humans
Hypoparathyroidism/diagnosis/*genetics/pathology
Middle Aged
Nuclear Proteins/*genetics
Parathyroid Hormone/*genetics
Phenotype
Polymorphism, Single Nucleotide
Receptors, Calcium-Sensing/*genetics
Registries
Republic of Korea
Transcription Factors/*genetics
Young Adult
Nuclear Proteins
Parathyroid Hormone
Receptors, Calcium-Sensing
Transcription Factors

Figure

• 

  Fig. 1 Filters used in analysis of the exome data and numbers of candidate variants.

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