Case report: A novel biallelic variant causing multisystem anomalies with severe epilepsy, widening the spectrum of syndrome
The fat mass and obesity-associated gene ( FTO ) codes for a DNA/RNA demethylase. Pathological variants in this gene are rare, with only three reports in the literature, all with mutations in the catalytic domain. We report the first biallelic human variant in fat mass and obesity-associated gene (c...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2023-07-01
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| Series: | SAGE Open Medical Case Reports |
| Online Access: | https://doi.org/10.1177/2050313X231188883 |
| _version_ | 1827890916849876992 |
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| author | Naomi Mayman Jiangbo Wei Shangjun Cai Rohan Soman Hillary Raynes Maite La Vega-Talbott Chuan He Thomas Naidich G. Praveen Raju Sathiji Kathiresu Nageshwaran |
| author_facet | Naomi Mayman Jiangbo Wei Shangjun Cai Rohan Soman Hillary Raynes Maite La Vega-Talbott Chuan He Thomas Naidich G. Praveen Raju Sathiji Kathiresu Nageshwaran |
| author_sort | Naomi Mayman |
| collection | DOAJ |
| description | The fat mass and obesity-associated gene ( FTO ) codes for a DNA/RNA demethylase. Pathological variants in this gene are rare, with only three reports in the literature, all with mutations in the catalytic domain. We report the first biallelic human variant in fat mass and obesity-associated gene (c.287G>C, p.Arg96Pro/R96P) outside the catalytic site, causing numerous abnormalities across multiple organ systems, affecting respiratory, cardiovascular, and neurological function. Biochemical assays of cells with the patient’s variant were performed to further quantify the effect of the variant on function. Loss-of-function resulting from the patient’s R96P missense variant was demonstrated with in vitro biochemical characterization of demethylase activity, resulting in a 90% reduction in function of the fat mass and obesity-associated protein compared to wild-type. Our findings demonstrate a novel fat mass and obesity-associated gene non-catalytic site variant with a unique patient phenotype of bilateral multifocal epilepsy and multisystem congenital anomalies. |
| first_indexed | 2024-03-12T21:16:25Z |
| format | Article |
| id | doaj.art-f75930d2cefe4b9a8cd20f0a011b5c90 |
| institution | Directory Open Access Journal |
| issn | 2050-313X |
| language | English |
| last_indexed | 2024-03-12T21:16:25Z |
| publishDate | 2023-07-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | SAGE Open Medical Case Reports |
| spelling | doaj.art-f75930d2cefe4b9a8cd20f0a011b5c902023-07-29T09:03:41ZengSAGE PublishingSAGE Open Medical Case Reports2050-313X2023-07-011110.1177/2050313X231188883Case report: A novel biallelic variant causing multisystem anomalies with severe epilepsy, widening the spectrum of syndromeNaomi Mayman0Jiangbo Wei1Shangjun Cai2Rohan Soman3Hillary Raynes4Maite La Vega-Talbott5Chuan He6Thomas Naidich7G. Praveen Raju8Sathiji Kathiresu Nageshwaran9Icahn School of Medicine at Mount Sinai, New York, NY, USADepartment of Chemistry, University of Chicago, IL, USADepartment of Chemistry, University of Chicago, IL, USAWeill Cornell/Rockefeller/Sloan Kettering MD/PhD Tri-institutional Program, New York, NY, USADepartment of Neurology, Mount Sinai, New York, NY, USADepartment of Neurology, Mount Sinai, New York, NY, USADepartment of Chemistry, University of Chicago, IL, USADepartment of Radiology, Mount Sinai, New York, NY, USADepartment of Neurology, Mount Sinai, New York, NY, USADepartment of Neurology, Mount Sinai, New York, NY, USAThe fat mass and obesity-associated gene ( FTO ) codes for a DNA/RNA demethylase. Pathological variants in this gene are rare, with only three reports in the literature, all with mutations in the catalytic domain. We report the first biallelic human variant in fat mass and obesity-associated gene (c.287G>C, p.Arg96Pro/R96P) outside the catalytic site, causing numerous abnormalities across multiple organ systems, affecting respiratory, cardiovascular, and neurological function. Biochemical assays of cells with the patient’s variant were performed to further quantify the effect of the variant on function. Loss-of-function resulting from the patient’s R96P missense variant was demonstrated with in vitro biochemical characterization of demethylase activity, resulting in a 90% reduction in function of the fat mass and obesity-associated protein compared to wild-type. Our findings demonstrate a novel fat mass and obesity-associated gene non-catalytic site variant with a unique patient phenotype of bilateral multifocal epilepsy and multisystem congenital anomalies.https://doi.org/10.1177/2050313X231188883 |
| spellingShingle | Naomi Mayman Jiangbo Wei Shangjun Cai Rohan Soman Hillary Raynes Maite La Vega-Talbott Chuan He Thomas Naidich G. Praveen Raju Sathiji Kathiresu Nageshwaran Case report: A novel biallelic variant causing multisystem anomalies with severe epilepsy, widening the spectrum of syndrome SAGE Open Medical Case Reports |
| title | Case report: A novel biallelic variant causing multisystem anomalies with severe epilepsy, widening the spectrum of syndrome |
| title_full | Case report: A novel biallelic variant causing multisystem anomalies with severe epilepsy, widening the spectrum of syndrome |
| title_fullStr | Case report: A novel biallelic variant causing multisystem anomalies with severe epilepsy, widening the spectrum of syndrome |
| title_full_unstemmed | Case report: A novel biallelic variant causing multisystem anomalies with severe epilepsy, widening the spectrum of syndrome |
| title_short | Case report: A novel biallelic variant causing multisystem anomalies with severe epilepsy, widening the spectrum of syndrome |
| title_sort | case report a novel biallelic variant causing multisystem anomalies with severe epilepsy widening the spectrum of syndrome |
| url | https://doi.org/10.1177/2050313X231188883 |
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