One pedigree analysis of a familial hypocalciuric hypercalcemia caused by a new heterozygous mutation in calcium-sensing receptor gene / 中华内分泌代谢杂志

ABSTRACT

Medical history and physical examinations were performed to assess the clinical manifestations and growth of one patient with familial hypocalciuric hypercalcemia(FHH). Clinical data, including histories of his parents and 3 maternal relatives were collected. Serum parathyroid hormone(PTH), calcium, phosphorus, 24-hour urinary calcium, and 24-hour urinary calcium to creatinine ratio(UCCR)were measured or calculated. Meanwhile, after peripheral blood samples were collected and genomic DNA was extracted, the whole exome sequencing to detect gene mutations of the proband was performed. Further family screenings were also performed by Sanger sequencing to assess the relationship between genotype and phenotype. The results showed that the proband with motor developmental delays had severe hypercalcemia(4.20 mmol/L), while his mother without clinical symptoms had a higher blood calcium within the normal range(2.57 mmol/L). However, their urinary calcium levels were both low(UCCR< 0.01). The C→T heterozygous missense mutation was found by exome sequencing at nucleotide 1243 within exon 4 of calcium sensing receptor(CaSR)gene in the proband, which caused a substitution of Arginine to Tryptophan(R415W). Sanger sequencing confirmed the same mutation in his mother. There was no mutation in other family members. (Chin J Endocrinol Metab, 2018, 34 583-586)