Mutations in the AP1S2 gene encoding the sigma 2 subunit of the adaptor protein 1 complex are associated with syndromic X-linked mental retardation with hydrocephalus and calcifications in basal ganglia
| Autor: | M. T. Iba-Zizen, Ginevra Zanni, V. des Portes, Jamel Chelly, Mary Porteous, Thierry Bienvenu, Delphine Héron, David T. Bonthron, J. L. Pedespan, C. Julien, Karine Poirier, C. Franconnet, L. Castelnau, Yoann Saillour, L. Guibaud |
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| Přispěvatelé: | Laboratoire sur le langage, le cerveau et la cognition (L2C2), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut des Nanosciences de Paris (INSP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL) |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Genetics
0303 health sciences medicine.medical_specialty Candidate gene Mutation [SCCO.NEUR]Cognitive science/Neuroscience Nonsense mutation Basal ganglia calcification Biology medicine.disease_cause 03 medical and health sciences Exon 0302 clinical medicine Endocrinology Internal medicine Molecular genetics medicine Letter to JMG 030217 neurology & neurosurgery Genetics (clinical) AP1S2 X chromosome 030304 developmental biology |
| Zdroj: | Journal of Medical Genetics Journal of Medical Genetics, 2007, 44 (11), pp.739-44. ⟨10.1136/jmg.2007.051334⟩ Journal of Medical Genetics, BMJ Publishing Group, 2007, 44 (11), pp.739-44. ⟨10.1136/jmg.2007.051334⟩ |
| ISSN: | 0022-2593 1468-6244 |
| DOI: | 10.1136/jmg.2007.051334⟩ |
| Popis: | International audience; Fried syndrome, first described in 1972, is a rare X-linked mental retardation that has been mapped by linkage to Xp22. Clinical characteristics include mental retardation, mild facial dysmorphism, calcifications of basal ganglia and hydrocephalus. A large four-generation family in which the affected males have striking clinical features of Fried syndrome were investigated for linkage to X-chromosome markers; the results showed that the gene for this condition lies within the interval DXS7109-DXS7593 in Xp22.2. In total, 60 candidate genes located in this region, including AP1S2, which was recently shown to be involved in mental retardation, were screened for mutations. A mutation in the third intron of AP1S2 was found in all affected male subjects in this large French family. The mutation resulted in skipping of exon 3, predicting a protein with three novel amino-acids and with termination at codon 64. In addition, the first known large Scottish family affected by Fried syndrome was reinvestigated, and a new nonsense mutation, p.Gln66X, was found in exon 3. Using CT, both affected patients from the French family who were analysed had marked calcifications of the basal ganglia, as previously observed in the first Scottish family, suggesting that the presence of distinctive basal ganglia calcification is an essential parameter to recognise this syndromic disorder. It may be possible to use this feature to identify families with X-linked mental retardation that should be screened for mutations in AP1S2. |
| Databáze: | OpenAIRE |
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