title: Genetics of pseudohypoparathyroidism types Ia and Ic.
abstract: Pseudohypoparathyroidism (PHP) types Ia and Ic result from heterozygous inactivating mutations of Gs alpha, the alpha-subunit of the heterotrimeric stimulatory G-protein, Gs. Both are characterized by a combination of Albright's hereditary osteodystrophy and, when the mutation is maternally inherited, end-organ resistance to multiple hormones. Due to complex tissue-specific imprinting of Gs alpha, paternally-derived mutations do not usually lead to hormone resistance. More than 100 mutations have been characterized in patients with PHP-Ia and one mutation in type Ic. These are scattered throughout the gene, with one significant mutational hotspot in exon 7. Identification of mutations in a clinical service setting is important for accurate genetic counselling and clinical management of affected families. However, only 70-80% of mutations are identified by direct sequencing of coding exons and splice junctions. Screening for whole exon deletions and intronic or regulatory mutations in mutation-negative families is therefore now an important priority to establish the full mutational spectrum in these conditions.
authors.affiliation: Division of Medical Genetics, University of Leicester and Leicestershire Genetics Service, University Hospitals of Leicester NHS Trust, Leicester, UK. aldredm@ccf.org
authors.forename: Micheala A
authors.initials: MA
authors.lastname: Aldred
mesh_terms: D005359:Fibrous Dysplasia, Polyostotic / Q000150:complications / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D040582:Inheritance Patterns; D009154:Mutation / Q000235:genetics*; D011547:Pseudohypoparathyroidism / Q000145:classification / Q000150:complications / Q000235:genetics*
chemical_list: D019205:GTP-Binding Protein alpha Subunits, Gs