PMID- 10523031
OWN - NLM
STAT- MEDLINE
DCOM- 19991104
LR  - 20061115
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 84
IP  - 10
DP  - 1999 Oct
TI  - A novel mutation of the signal peptide of the preproparathyroid hormone gene
      associated with autosomal recessive familial isolated hypoparathyroidism.
PG  - 3792-6
AB  - 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.
FAU - Sunthornthepvarakul, T
AU  - Sunthornthepvarakul T
AD  - Department of Medicine, Rajavithi Hospital, Bangkok, Thailand.
      thongkum@rajavithi.go.th
FAU - Churesigaew, S
AU  - Churesigaew S
FAU - Ngowngarmratana, S
AU  - Ngowngarmratana S
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Parathyroid Hormone)
RN  - 0 (Protein Precursors)
RN  - 0 (Protein Sorting Signals)
RN  - 67418-29-5 (preproparathormone)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Amino Acid Sequence/genetics
MH  - Base Sequence/genetics
MH  - DNA/genetics
MH  - Female
MH  - *Genes, Recessive
MH  - Humans
MH  - Hypoparathyroidism/*genetics
MH  - Infant
MH  - Infant, Newborn
MH  - Molecular Sequence Data
MH  - Mutation/*genetics
MH  - Parathyroid Hormone/*genetics
MH  - Pedigree
MH  - Protein Precursors/*genetics
MH  - Protein Sorting Signals/*genetics
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - 10.1210/jcem.84.10.6070 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1999 Oct;84(10):3792-6. doi: 10.1210/jcem.84.10.6070.