Preliminary localization of a gene for autosomal dominant hypoparathyroidism to chromosome 3q13.
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 3q13. A maximum lod score of 2.71 at theta = 0.0 was observed with marker D3S1303. Positive lod scores were observed at theta = 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 theta = 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 theta = 0.0 by chance was 1 in 1000. The data presented above provide important preliminary evidence supporting linkage to chromosome 3q13. This region contains a Ca(2+)-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 Ca(2+)-sensing receptor suppressing PTH secretion and lowering the "set point" for serum calcium levels.
Finegold
D N
DN
Department of Pediatrics, School of Medicine, University of Pittsburgh, Pennsylvania 15261.
Armitage
M M
MM
Galiani
M
M
Matise
T C
TC
Pandian
M R
MR
Perry
Y M
YM
Deka
R
R
Ferrell
R E
RE
D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D005799:Genes, Dominant; D005815:Genetic Code; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007011:Hypoparathyroidism / Q000235:genetics*; D007223:Infant; D008297:Male; D009690:Nucleic Acid Conformation; D010281:Parathyroid Hormone / Q000235:genetics; D010641:Phenotype
D005819:Genetic Markers; D010281:Parathyroid Hormone