التفاصيل البيبلوغرافية
| العنوان: |
Widespread genomic influences on phenotype in Dravet syndrome, a 'monogenic' condition. |
| المؤلفون: |
Custodio, Helena Martins, Clayton, Lisa M, Bellampalli, Ravishankara, Pagni, Susanna, Silvennoinen, Katri, Caswell, Richard, Consortium, Genomics England Research, Brunklaus, Andreas, Guerrini, Renzo, Koeleman, Bobby P C, Lemke, Johannes R, Møller, Rikke S, Scheffer, Ingrid E, Weckhuysen, Sarah, Zara, Federico, Zuberi, Sameer, Kuchenbaecker, Karoline, Balestrini, Simona, Mills, James D, Sisodiya, Sanjay M |
| المصدر: |
Brain: A Journal of Neurology; Sep2023, Vol. 146 Issue 9, p3885-3897, 13p |
| مصطلحات موضوعية: |
EPILEPSY, FOCAL cortical dysplasia, DISEASE risk factors, MONOGENIC & polygenic inheritance (Genetics), PHENOTYPES, EARLY death |
| مستخلص: |
Dravet syndrome is an archetypal rare severe epilepsy, considered 'monogenic', typically caused by loss-of-function SCN1A variants. Despite a recognizable core phenotype, its marked phenotypic heterogeneity is incompletely explained by differences in the causal SCN1A variant or clinical factors. In 34 adults with SCN1A -related Dravet syndrome, we show additional genomic variation beyond SCN1A contributes to phenotype and its diversity, with an excess of rare variants in epilepsy-related genes as a set and examples of blended phenotypes, including one individual with an ultra-rare DEPDC5 variant and focal cortical dysplasia. The polygenic risk score for intelligence was lower, and for longevity, higher, in Dravet syndrome than in epilepsy controls. The causal, major-effect, SCN1A variant may need to act against a broadly compromised genomic background to generate the full Dravet syndrome phenotype, whilst genomic resilience may help to ameliorate the risk of premature mortality in adult Dravet syndrome survivors. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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