New mechanisms involved in paternal 20q disomy associated with pseudohypoparathyroidism
| Autor: | Ana Bernal Chico, Luis Castaño, Guiomar Perez de Nanclares, Edelmiro Menéndez Torre, Fernando Goñi Goicoechea, EDUARDO FERNANDEZ-REBOLLO, Loreto Martorell, Liliana Del Carmen Suárez Santa Cruz, Diego Yeste, CARMEN GUILLEN PONCE, Jesús Argente, Aurora Sanchez Diaz, Ignacio Diez Lopez, Encarna Guillén-Navarro, SONIA GAZTAMBIDE, LUCIA SENTCHORDI |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male musculoskeletal diseases Proband medicine.medical_specialty Mitotic crossover Endocrinology Diabetes and Metabolism Chromosomes Human Pair 20 Parathyroid Hormone Resistance Methylation Polymorphism Single Nucleotide Endocrinology Internal medicine Chromogranins GTP-Binding Protein alpha Subunits Gs GNAS complex locus medicine Humans Pseudohypoparathyroidism Genetics biology General Medicine Middle Aged Uniparental Disomy medicine.disease Uniparental disomy Child Preschool biology.protein Female STX16 Chromosome 20 Microsatellite Repeats |
| Zdroj: | European Journal of Endocrinology. 163:953-962 |
| ISSN: | 1479-683X 0804-4643 |
| DOI: | 10.1530/eje-10-0435 |
| Popis: | PurposeType I pseudohypoparathyroidism (PHP-I) can be subclassified into Ia and Ib, depending on the presence or absence of Albright's hereditary osteodystrophy's phenotype, diminished α-subunit of the stimulatory G protein (Gsα) activity and multihormonal resistance. Whereas PHP-Ia is mainly associated with heterozygous inactivating mutations in Gsα-coding exons ofGNAS, PHP-Ib is caused by imprinting defects ofGNAS. To date, just one patient with PHP and complete paternal uniparental disomy (UPD) has been described.We sought to identify the underlining molecular defect in twenty patients with parathyroid hormone resistance, hypocalcemia and hyperphosphatemia, and abnormal methylation pattern at GNAS locus.MethodsMicrosatellite typing and comparative genome hybridization were performed for proband and parents.ResultsWe describe four patients with partial paternal UPD of chromosome 20 involving pat20qUPD in one case, from 20q13.13-qter in two cases, and pat20p heterodisomy plus interstitial 20q isodisomy in one patient.ConclusionsThese observations demonstrate that mitotic recombination of chromosome 20 can also give rise to UPD and PHP, a situation similar to other imprinting disorders, such as Beckwith–Wiedemann syndrome or neonatal diabetes. |
| Databáze: | OpenAIRE |
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