![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
|
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
3MB | |
![[img]](http://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Material)
5MB |
| Item Type: | Article |
|---|---|
| Title: | Broadening the phenotypic and molecular spectrum of FINCA syndrome: Biallelic NHLRC2 variants in 15 novel individuals |
| Creators Name: | Sczakiel, H.L. and Zhao, M. and Wollert-Wulf, B. and Danyel, M. and Ehmke, N. and Stoltenburg, C. and Damseh, N. and Al-Ashhab, M. and Balci, T.B. and Osmond, M. and Andrade, A. and Schallner, J. and Porrmann, J. and McDonald, K. and Liao, M. and Oppermann, H. and Platzer, K. and Dierksen, N. and Mojarrad, M. and Eslahi, A. and Bakaeean, B. and Calame, D.G. and Lupski, J.R. and Firoozfar, Z. and Seyedhassani, S.M. and Mohammadi, S.A. and Anwaar, N. and Rahman, F. and Seelow, D. and Janz, M. and Horn, D. and Maroofian, R. and Boschann, F. |
| Abstract: | FINCA syndrome [MIM: 618278] is an autosomal recessive multisystem disorder characterized by fibrosis, neurodegeneration and cerebral angiomatosis. To date, 13 patients from nine families with biallelic NHLRC2 variants have been published. In all of them, the recurrent missense variant p.(Asp148Tyr) was detected on at least one allele. Common manifestations included lung or muscle fibrosis, respiratory distress, developmental delay, neuromuscular symptoms and seizures often followed by early death due to rapid disease progression.Here, we present 15 individuals from 12 families with an overlapping phenotype associated with nine novel NHLRC2 variants identified by exome analysis. All patients described here presented with moderate to severe global developmental delay and variable disease progression. Seizures, truncal hypotonia and movement disorders were frequently observed. Notably, we also present the first eight cases in which the recurrent p.(Asp148Tyr) variant was not detected in either homozygous or compound heterozygous state.We cloned and expressed all novel and most previously published non-truncating variants in HEK293-cells. From the results of these functional studies, we propose a potential genotype-phenotype correlation, with a greater reduction in protein expression being associated with a more severe phenotype.Taken together, our findings broaden the known phenotypic and molecular spectrum and emphasize that NHLRC2-related disease should be considered in patients presenting with intellectual disability, movement disorders, neuroregression and epilepsy with or without pulmonary involvement. |
| Keywords: | Disease Progression, Fibrosis, HEK293 Cells, Intellectual Disability, Movement Disorders, Phenotype, Seizures, Syndrome |
| Source: | European Journal of Human Genetics |
| ISSN: | 1018-4813 |
| Publisher: | Nature Publishing Group |
| Volume: | 31 |
| Number: | 8 |
| Page Range: | 905-317 |
| Date: | August 2023 |
| Official Publication: | https://doi.org/10.1038/s41431-023-01382-0 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
Download Statistics
Download Statistics
