A novel mutation of the signal peptide of the preproparathyroid hormone gene associated with autosomal recessive familial isolated hypoparathyroidism

被引:72
作者
Sunthornthepvarakul, T [1 ]
Churesigaew, S
Ngowngarmratana, S
机构
[1] Mahidol Univ, Ramathibodi Hosp, Dept Med, Bangkok 10400, Thailand
[2] Queen Sirikit Natl Inst Child Hlth, Dept Pediat, Bangkok 10400, Thailand
关键词
D O I
10.1210/jc.84.10.3792
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We report a novel mutation of the signal peptide of the prepro-PTH gene associated with autosomal recessive familial isolated hypoparathyroidism. The proposita presented with neonatal hypocalcemic seizures. Serum calcium was 1.5 mmol/L (normal, 2.0-2.5); phosphate was 3.6 mmol/L (normal, 0.9-1.5). She was born to consanguineous parents. A few years later, 2 younger sisters and her niece presented with neonatal hypocalcemic seizures. Their intact PTH levels were undetectable during severe hypocalcemia. Genomic DNA from the proposita was sequenced all exons of the prepro-PTH gene. A replacement of thymine with a cytosine was found in the first nucleotide of position 23 in the 25-amino acid signal peptide. This results in the replacement of the normal Ser (TCG) with a Pro (CCG). Genotyping of family members was carried out by identification of a new MspI site created by the mutation. Only affected family members were homozygous for the mutant allele, whereas the parents were heterozygous, supporting autosomal recessive inheritance. As this mutation is at the -3 position in the signal peptide of the prepro-PTH gene, we hypothesized that the prepro-PTH mutant might not be cleaved by signal peptidase at the normal position, and it might be degraded in rough endoplasmic reticulum.
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页码:3792 / 3796
页数:5
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