title: Genetic and clinical characteristics of korean patients with isolated hypoparathyroidism: from the Korean hypopara registry study.
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.
authors.affiliation: Department of Internal Medicine, Cheil General Hospital, Kwandong University College of Medicine, Seoul, Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Park
authors.forename: Young Sil
authors.initials: YS
authors.lastname: Eom
authors.forename: Byoungho
authors.initials: B
authors.lastname: Choi
authors.forename: Hyon-Seung
authors.initials: HS
authors.lastname: Yi
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Yu
authors.forename: Kiyoung
authors.initials: K
authors.lastname: Lee
authors.forename: Hyun-Seok
authors.initials: HS
authors.lastname: Jin
authors.forename: Yoon-Sok
authors.initials: YS
authors.lastname: Chung
authors.forename: Tae Sik
authors.initials: TS
authors.lastname: Jung
authors.forename: Sihoon
authors.initials: S
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D015331:Cohort Studies; D006579:Heterozygote; D006801:Humans; D007011:Hypoparathyroidism / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010281:Parathyroid Hormone / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044169:Receptors, Calcium-Sensing / Q000235:genetics*; D012042:Registries; D056910:Republic of Korea; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: C095550:CASR protein, human; C119532:GCM2 protein, human; D009687:Nuclear Proteins; D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D014157:Transcription Factors
keywords: CASR; GCMB; Hypocalcemia; Hypoparathyroidism; Prepro-PTH