TY  - JOUR
AU  - Tőke, Judit
AU  - Czirják, Gábor
AU  - Patócs, Attila Balázs
AU  - Enyedi, Balázs
AU  - Gergics, Péter
AU  - Csákváry, Violetta
AU  - Enyedi, Péter
AU  - Tóth, Miklós
TI  - Neonatal severe hyperparathyroidism associated with a novel de novo heterozygous R551K inactivating mutation and a heterozygous A986S polymorphism of the calcium-sensing receptor gene
JF  - CLINICAL ENDOCRINOLOGY
J2  - CLIN ENDOCRINOL
VL  - 67
PY  - 2007
IS  - 3
SP  - 385
EP  - 392
PG  - 8
SN  - 0300-0664
DO  - 10.1111/j.1365-2265.2007.02896.x
UR  - https://m2.mtmt.hu/api/publication/1134778
ID  - 1134778
AB  - Introduction: Neonatal severe hyperparathyroidism (NSHPT) is induced by inactivating mutations of human calcium-sensing receptor (CaSR). Only three heterozygous de novo inactivating mutations of CaSR causing NSHPT have been described. We report the case of a now 11-year-old boy with NSHPT and we characterize a novel inactivating mutation along with the results of some functional analyses. Patient and methods: As a neonate the patient presented the clinical syndrome of NSHPT. At 6 years of age persisting hypercalcaemia without clinical symptoms was documented, and the patient remained completely symptom free without parathyroid surgery until his present age of 11 years. The entire coding region of the CaSR gene of the patient and his family members was sequenced. Functional investigation was performed in HEK-293 cells, transiently transfected with wild type and mutant CaSR plasmid constructs. Results: Sequence analysis revealed a novel de novo heterozygous mutation at codon 551 (AGG?AAG), predicting a change of arginine to lysine (R551K) and a known heterozygous polymorphism (A986S) on the same allele, which was inherited from the father. We demonstrated that the novel R551K mutation significantly reduced the calcium sensitivity of CaSR (EC50: from 3.38 ? 0.62-6.10 ? 0.83 mmol/l), which was not alleviated by the simultaneous presence of A986S polymorphism. Conclusions: We present the fourth NSHPT case induced by a novel de novo heterozygous inactivating mutation (R551K) of the CaSR gene. The disease gradually reverted to a symptomless, benign condition resembling familial hypocalciuric hypercalcaemia without any surgical intervention. ? 2007 The Authors.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Takács, István
AU  - Speer, Gábor
AU  - Bajnok, Éva
AU  - Tabák, Ádám
AU  - Nagy, Zsolt
AU  - Horváth, Csaba
AU  - Kovacs, K
AU  - Lakatos, Péter
TI  - Lack of association between calcium-sensing receptor gene "A986S" polymorphism and bone mineral density in Hungarian postmenopausal women.
JF  - BONE
J2  - BONE
VL  - 30
PY  - 2002
IS  - 6
SP  - 849
EP  - 852
PG  - 4
SN  - 8756-3282
DO  - 10.1016/S8756-3282(02)00741-X
UR  - https://m2.mtmt.hu/api/publication/1335565
ID  - 1335565
AB  - Calcium-sensing receptor (CaSR) is an attractive candidate gene for osteoporosis susceptibility. The CaSR "A986S" genotype has been shown to have an effect on serum calcium. Recently, an association has been reported between the CaSR gene A986S polymorphism and bone mineral density in healthy white girls. In this study, we examined whether CaSR gene A986S polymorphism is associated with decreased bone mass in 230 Hungarian postmenopausal women. From this cohort, 108 osteoporotic patients were compared with 122 healthy control women. Bone mineral density (BMD) was measured at the lumbar spine (L2-4) and femoral neck using dual-energy X-ray absorptiometry. Allele-specific polymerase chain reaction was used to amplify A986S polymorphisms of the CaSR gene. We found no difference in the distribution of different alleles or genotypes between groups (p = 0.762). No significant effect of CaSR genotype on BMD was observed either in the whole population or in the subgroups. Our data do not support the idea that CaSR gene A986S polymorphism has an impact on bone mass.
LA  - English
DB  - MTMT
ER  -