The gene responsible for pseudohypoparathyroidism type Ib is paternally imprinted and maps in four unrelated kindreds to chromosome 20q13.3.
نویسندگان
چکیده
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.
منابع مشابه
Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS.
Patients with pseudohypoparathyroidism type Ib (PHP-Ib) have hypocalcemia and hyperphosphatemia due to renal parathyroid hormone (PTH) resistance, but lack physical features of Albright hereditary osteodystrophy. PHP-Ib is thus distinct from PHP-Ia, which is caused by mutations in the GNAS exons encoding the G protein alpha subunit. However, an imprinted autosomal dominant form of PHP-Ib (AD-PH...
متن کاملGNAS locus and pseudohypoparathyroidism.
Pseudohypoparathyroidism (PHP) is characterized by hypocalcemia and hyperphosphatemia due to resistance to parathyroid hormone (PTH). Patients with PHP-Ia often present with additional hormonal resistance and show characteristic physical features that are collectively termed Albright's hereditary osteodystrophy (AHO). These features are also present in pseudopseudohypoparathyroidism (PPHP), but...
متن کاملMolecular diagnosis of pseudohypoparathyroidism type Ib in a family with presumed paroxysmal dyskinesia.
We describe 2 sisters diagnosed initially with paroxysmal kinesigenic choreoathetosis, a condition characterized by brief episodes of spasms precipitated by sudden movement. However, subsequent testing showed hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone levels consistent with pseudohypoparathyroidism type Ib. This diagnosis was confirmed by genetic testing, which identified...
متن کاملGNAS Mutations in Pseudohypoparathyroidism Type 1a and Related Disorders
Pseudohypoparathyroidism type 1a (PHP1a) is characterized by hypocalcaemia and hyperphosphatemia due to parathyroid hormone resistance, in association with the features of Albright's hereditary osteodystrophy (AHO). PHP1a is caused by maternally inherited inactivating mutations of Gs-alpha, which is encoded by a complex imprinted locus termed GNAS. Paternally inherited mutations can lead either...
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Background Genomic imprinting is a heritable and developmentally essential phenomenon by which gene expression occurs in an allele-specific manner1. While the imprinted alleles are primarily silenced by DNA methylation, it remains largely unknown how methylation is targeted to imprinting control region (ICR), also called differentially methylated region (DMR), and maintained. Here we show that ...
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ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 95 20 شماره
صفحات -
تاریخ انتشار 1998