{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T20:44:22Z","timestamp":1787604262167,"version":"build-2736575974"},"reference-count":23,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u20132.5); phosphate was 3.6 mmol\/L (normal, 0.9\u20131.5). 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\u2212 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.<\/jats:p>","DOI":"10.1210\/jcem.84.10.6070","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:03:58Z","timestamp":1389200638000},"page":"3792-3796","source":"Crossref","is-referenced-by-count":5,"title":["A Novel Mutation of the Signal Peptide of the Preproparathyroid Hormone Gene Associated with Autosomal Recessive Familial Isolated Hypoparathyroidism*"],"prefix":"10.1210","volume":"84","author":[{"given":"Thongkum","family":"Sunthornthepvarakul","sequence":"first","affiliation":[{"name":"Department of Medicine, Rajavithi Hospital (T.S., S.N.), Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunchai","family":"Churesigaew","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Queen Sirikit National Institute of Child Health (S.C.), Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supunnee","family":"Ngowngarmratana","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rajavithi Hospital (T.S., S.N.), Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613465552400_R1","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/BF01574261","article-title":"Human parathyroid hormone gene (PTH) is on short arm of chromosome 11.","volume":"9","author":"Nayler","year":"1983","journal-title":"Somat Cell Genet"},{"key":"2020071613465552400_R2","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1152\/physrev.1984.64.3.985","article-title":"Parathyroid hormone: biochemical aspects of biosynthesis, secretion, action, and metabolism.","volume":"64","author":"Habener","year":"1984","journal-title":"Physiol Rev"},{"key":"2020071613465552400_R3","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1172\/JCI114811","article-title":"Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism.","volume":"86","author":"Arnold","year":"1990","journal-title":"J Clin Invest"},{"key":"2020071613465552400_R4","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/ng0592-149","article-title":"A donor splice site mutation in the parathyroid hormone gene is associated with autosomal recessive hypoparathyroidism.","volume":"1","author":"Parkinson","year":"1992","journal-title":"Nat Genet"},{"key":"2020071613465552400_R5","doi-asserted-by":"crossref","first-page":"4683","DOI":"10.1093\/nar\/14.11.4683","article-title":"A new method for predicting signal sequence cleavage sites.","volume":"14","year":"1986","journal-title":"Nucleic Acids Res"},{"key":"2020071613465552400_R6","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/297647a0","article-title":"Secretory protein translocation across membrane\u2013the role of the \u201cdocking protein.\u201d","volume":"297","author":"Meyer","year":"1982","journal-title":"Nature"},{"key":"2020071613465552400_R7","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/0968-0004(90)90076-N","article-title":"Protein transport across the ER membrane.","volume":"15","year":"1990","journal-title":"Trends Biochem Sci"},{"key":"2020071613465552400_R8","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/0092-8674(90)90096-W","article-title":"Microtubule-dependent retrograde transport of proteins into the ER in the presence of brefeldin A suggests an ER recycling pathway.","volume":"60","author":"Lippincott-Schwart","year":"1990","journal-title":"Cell"},{"key":"2020071613465552400_R9","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0022-2836(85)90046-4","article-title":"Signal sequences: the limits of variation.","volume":"184","year":"1985","journal-title":"J Mol Biol"},{"key":"2020071613465552400_R10","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S0022-2836(83)80341-6","article-title":"A putative signal peptidase recognition site and sequence in eukaryotic and prokaryotic signal peptides.","volume":"167","author":"Perlman","year":"1983","journal-title":"J Mol Biol"},{"key":"2020071613465552400_R11","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1083\/jcb.91.2.557","article-title":"Translocation of proteins across the endoplasmic reticulum. 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