A large family in which hypoparathyroidism was observed to segregate as an autosomal dominant trait in three generations was identified. Mutation in the PTH gene was excluded by linkage and single-stranded conformational analysis. The hypocalcemic phenotype in this family was mapped by linkage analysis using short, tandem-repeat polymorphisms to the region of chromosome 3ql3. A maximum lod score of 2.71 at 0 = 0.0 was observed with marker D3S1303. Positive lod scores were observed at 0 = 0.0 with markers flanking D3S1303. Multipoint linkage analysis gave a lod score of 2.71 for the region flanking D3S1303. Simulation using the computer program SLINK showed that a lod score of 2.71 at 0 = 0.0 was. the maximum lod score possible given the pedigree structure. The simulation also showed that given the structure of the pedigree the probability of observing a lod score of 2.71 at 0 = 0.0 by chance was 1 in 1000. The data presented above provide important preliminary evidence supporting linkage to chromosome 3ql3. This region contains a Ca2+-sensing receptor gene that is proposed as a key signal transduction element for changes in extracellular Ca2+ concentrations in mechanisms of regulation of PTH secretion from parathyroid cells. The mutation in this family may activate the Ca2+-sensing receptor suppressing PTH secretion and lowering the "set point" for serum calcium levels.
All Science Journal Classification (ASJC) codes
- Pediatrics, Perinatology, and Child Health