The gene responsible for pseudohypoparathyroidism type Ib is paternally imprinted and maps in four unrelated kindreds to chromosome 20q13.3.
Hypocalcemia and hyperphosphatemia caused by parathyroid hormone (PTH)-resistance are the only discernible abnormalities in pseudohypoparathyroidism type Ib (PHP-Ib). Because mutations in the PTH/PTH-related peptide receptor, a plausible candidate gene, had been excluded previously, we conducted a genome-wide search with four PHP-Ib kindreds and established linkage to a small telomeric region on chromosome 20q, which contains the stimulatory G protein gene. We, furthermore, showed that the genetic defect is imprinted paternally and thus is inherited in the same mode as the PTH-resistant hypocalcemia in kindreds with PHP-Ia and/or pseudo-pseudohypoparathyroidism, two related disorders caused by different stimulatory G protein mutations.
Jüppner
H
H
Endocrine, Departments of Medicine and Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. jueppner@helix.mgh.harvard.edu
Schipani
E
E
Bastepe
M
M
Cole
D E
DE
Lawson
M L
ML
Mannstadt
M
M
Hendy
G N
GN
Plotkin
H
H
Koshiyama
H
H
Koh
T
T
Crawford
J D
JD
Olsen
B R
BR
Vikkula
M
M
D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D008040:Genetic Linkage; D018392:Genomic Imprinting; D006239:Haplotypes; D006801:Humans; D006996:Hypocalcemia / Q000235:genetics; D008126:Lod Score; D008297:Male; D009154:Mutation; D010375:Pedigree; D011547:Pseudohypoparathyroidism / Q000145:classification / Q000235:genetics*
D019204:GTP-Binding Proteins