J Korean Med Sci.  2010 Feb;25(2):317-320. 10.3346/jkms.2010.25.2.317.

Autosomal Dominant Hypocalcemia Caused by an Activating Mutation of the Calcium-Sensing Receptor Gene: The First Case Report in Korea

• Kim MY
• Tan AH
• Ki CS
• Lee JI
• Jang HW
• Shin HW
• Kim SW
• Min YK
• Lee MS
• Lee MK
• Kim KW
• Chung JH

• KMID: 1779268
• DOI: http://doi.org/10.3346/jkms.2010.25.2.317

Abstract

Hypoparathyroidism is an abnormality of calcium metabolism characterized by low serum levels of parathyroid hormone in spite of hypocalcemia. The causes of hypoparathyroidism are numerous. Activating mutations in the calcium-sensing receptor (CaSR) gene are well-known causes of familial isolated hypoparathyroidism, also known as autosomal dominant hypocalcemia (ADH). Here we describe members of a Korean family with a heterozygous Pro221Leu mutation causing ADH. This case is the first report in Korea.

Keyword

Hypoparathyroidism; Hypocalcemia; Receptors, Calcium-Sensing

MeSH Terms

Bone Density Conservation Agents/therapeutic use
Calcium Carbonate/therapeutic use
Female
Heterozygote
Humans
Hydroxycholecalciferols/therapeutic use
Hypocalcemia/diagnosis/drug therapy/*genetics
Mutation
Parathyroid Hormone/analysis
Pedigree
Receptors, Calcium-Sensing/*genetics
Republic of Korea
Sequence Analysis, DNA
Young Adult
Bone Density Conservation Agents
Hydroxycholecalciferols
Parathyroid Hormone
Receptors, Calcium-Sensing
Calcium Carbonate

Figure

• 

  Fig. 1 The pedigree of the family. One of the uncles deceased in his third decade without clear cause. Closed black circles indicate the affected persons (proband, sibling, and father). The arrow indicates the proband. Closed gray circle indicates proband's mother without mutation in calcium-sensing receptor (CaSR) gene. The remaining members of the family (open circles) were not included in this study because of inaccessibility.

• 

  Fig. 2 Direct sequencing of the calcium-sensing receptor (CaSR) gene.

Reference

1. Thakker RV. The Molecular genetics of Hypoparathyroidism. The Parathyroids: basic and clinical concepts. 2001. 2nd ed. San Diego, CA: Academic Press;779–790.

2. Thakker RV. Genetics of endocrine and metabolic disorders: parathyroid. Rev Endocr Metab Disord. 2004. 5:37–51.

3. Pearce SH, Williamson C, Kifor O, Bai M, Coulthard MG, Davies M, Lewis-Barned N, McCredie D, Powell H, Kendall-Taylor P, Brown EM, Thakker RV. A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor. N Engl J Med. 1996. 335:1115–1122.

4. Pollak MR, Brown EM, Estep HL, McLaine PN, Kifor O, Park J, Hebert SC, Seidman CE, Seidman JG. Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation. Nat Genet. 1994. 8:303–307.

5. Arnold A, Horst SA, Gardella TJ, Baba H, Levine MA, Kronenberg HM. Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism. J Clin Invest. 1990. 86:1084–1087.

6. Chiu WY, Chen HW, Chao HW, Yann LT, Tsai KS. Identification of three novel mutations in the GATA3 gene responsible for familial hypoparathyroidism and deafness in the Chinese population. J Clin Endocrinol Metab. 2006. 91:4587–4592.

7. Brown EM, Pollak M, Chou YH, Seidman CE, Seidman JG, Hebert SC. Cloning and functional characterization of extracellular Ca(2+)-sensing receptors from parathyroid and kidney. Bone. 1995. 17:2 Suppl. 7S–11S.

8. Brown EM, Pollak M, Seidman CE, Seidman JG, Chou YH, Riccardi D, Hebert SC. Calcium-ion-sensing cell-surface receptors. N Engl J Med. 1995. 333:234–240.

9. Hendy GN, D'Souza-Li L, Yang B, Canaff L, Cole DE. Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia. Hum Mutat. 2000. 16:281–296.

10. Pidasheva S, D'Souza-Li L, Canaff L, Cole DE, Hendy GN. CASRdb: calcium-sensing receptor locus-specific database for mutations causing familial (benign) hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia. Hum Mutat. 2004. 24:107–111.

11. Conley YP, Finegold DN, Peters DG, Cook JS, Oppenheim DS, Ferrell RE. Three novel activating mutations in the calcium-sensing receptor responsible for autosomal dominant hypocalcemia. Mol Genet Metab. 2000. 71:591–598.

12. Lienhardt A, Bai M, Lagarde JP, Rigaud M, Zhang Z, Jiang Y, Kottler ML, Brown EM, Garabédian M. Activating mutations of the calcium-sensing receptor: management of hypocalcemia. J Clin Endocrinol Metab. 2001. 86:5313–5323.

13. Woo SI, Song H, Song KE, Kim DJ, Lee KW, Kim SJ, Chung YS. A case report of familial benign hypocalciuric hypercalcemia: a mutation in the calcium-sensing receptor gene. Yonsei Med J. 2006. 47:255–258.