Genetic and Clinical Characteristics of Korean Patients with Isolated Hypoparathyroidism: From the Korean Hypopara Registry Study.
10.3346/jkms.2013.28.10.1489
- Author:
So Young PARK
1
;
Young Sil EOM
;
Byoungho CHOI
;
Hyon Seung YI
;
Seung Hee YU
;
Kiyoung LEE
;
Hyun Seok JIN
;
Yoon Sok CHUNG
;
Tae Sik JUNG
;
Sihoon LEE
Author Information
1. Department of Internal Medicine, Cheil General Hospital, Kwandong University College of Medicine, Seoul, Korea.
- Publication Type:Case Reports
- Keywords:
CASR;
GCMB;
Hypocalcemia;
Hypoparathyroidism;
Prepro-PTH
- MeSH:
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
- From:Journal of Korean Medical Science
2013;28(10):1489-1495
- CountryRepublic of Korea
- Language:English
-
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.
