Congenital disorder of glycosylation with defective fucosylation 2 (FCSK gene defect): The third report in the literature with a mild phenotype
Abstract Background Congenital disorders of glycosylation (CDG) are a group of heterogeneous disorders caused by abnormal lipid or protein glycosylation. Variants in the FCSK gene have been reported to cause CDG. Defective FCSK‐induced CDG (FCSK–CDG) has only been reported previously in three unrela...
| Những tác giả chính: | , , , , , , , , , , , |
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| Định dạng: | Bài viết |
| Ngôn ngữ: | English |
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Wiley
2023-04-01
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| Loạt: | Molecular Genetics & Genomic Medicine |
| Những chủ đề: | |
| Truy cập trực tuyến: | https://doi.org/10.1002/mgg3.2117 |
| _version_ | 1827968233674637312 |
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| author | Abeer Al Tuwaijri Yusra Alyafee Muhammad Umair Arwa Alsubait Mashael Alharbi Hamad AlEidi Mariam Ballow Mohammed Aldrees Qamre Alam Abdulkareem Al Abdulrahman Muhammad Talal Alrifai Majid Alfadhel |
| author_facet | Abeer Al Tuwaijri Yusra Alyafee Muhammad Umair Arwa Alsubait Mashael Alharbi Hamad AlEidi Mariam Ballow Mohammed Aldrees Qamre Alam Abdulkareem Al Abdulrahman Muhammad Talal Alrifai Majid Alfadhel |
| author_sort | Abeer Al Tuwaijri |
| collection | DOAJ |
| description | Abstract Background Congenital disorders of glycosylation (CDG) are a group of heterogeneous disorders caused by abnormal lipid or protein glycosylation. Variants in the FCSK gene have been reported to cause CDG. Defective FCSK‐induced CDG (FCSK–CDG) has only been reported previously in three unrelated children. Methods In this study, we genetically and clinically examined a 3‐year‐old proband with resolved infantile spasms and normal development. Standard whole‐exome sequencing (WES) and Sanger sequencing were performed to identify the functional impact of the variant. Results WES revealed a rare biallelic missense variant (c.3013G>C; p.Val1005Leu) in FCSK. RT‐qPCR showed a significant depletion in FCSK gene expression in the affected individual. Western blotting revealed reduced FCSK expression at the protein level compared to that in the control. Furthermore, 3D protein modeling suggested changes in the secondary structure, which might affect the overall FCSK protein function. Conclusion This study broadens the mutation and phenotypic spectrum of FCSK‐associated developmental disorders. |
| first_indexed | 2024-04-09T18:18:54Z |
| format | Article |
| id | doaj.art-749d1d3869cd49fbb491ca3b51a3fe3b |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-09T18:18:54Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-749d1d3869cd49fbb491ca3b51a3fe3b2023-04-12T15:07:56ZengWileyMolecular Genetics & Genomic Medicine2324-92692023-04-01114n/an/a10.1002/mgg3.2117Congenital disorder of glycosylation with defective fucosylation 2 (FCSK gene defect): The third report in the literature with a mild phenotypeAbeer Al Tuwaijri0Yusra Alyafee1Muhammad Umair2Arwa Alsubait3Mashael Alharbi4Hamad AlEidi5Mariam Ballow6Mohammed Aldrees7Qamre Alam8Abdulkareem Al Abdulrahman9Muhammad Talal Alrifai10Majid Alfadhel11Medical Genomics Research Department King Abdullah International Medical Research Center (KAIMRC) Riyadh Saudi ArabiaMedical Genomics Research Department King Abdullah International Medical Research Center (KAIMRC) Riyadh Saudi ArabiaMedical Genomics Research Department King Abdullah International Medical Research Center (KAIMRC) Riyadh Saudi ArabiaKing Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG‐HA) Riyadh Saudi ArabiaMedical Genomics Research Department King Abdullah International Medical Research Center (KAIMRC) Riyadh Saudi ArabiaMedical Genomics Research Department King Abdullah International Medical Research Center (KAIMRC) Riyadh Saudi ArabiaMedical Genomics Research Department King Abdullah International Medical Research Center (KAIMRC) Riyadh Saudi ArabiaMedical Genomics Research Department King Abdullah International Medical Research Center (KAIMRC) Riyadh Saudi ArabiaMedical Genomics Research Department King Abdullah International Medical Research Center (KAIMRC) Riyadh Saudi ArabiaMedical Genomics Research Department King Abdullah International Medical Research Center (KAIMRC) Riyadh Saudi ArabiaNeurology Division, Department of Pediatrics King Abdulaziz Medical City, Ministry of National Guard Health Affairs (NGHA) Riyadh Saudi ArabiaMedical Genomics Research Department King Abdullah International Medical Research Center (KAIMRC) Riyadh Saudi ArabiaAbstract Background Congenital disorders of glycosylation (CDG) are a group of heterogeneous disorders caused by abnormal lipid or protein glycosylation. Variants in the FCSK gene have been reported to cause CDG. Defective FCSK‐induced CDG (FCSK–CDG) has only been reported previously in three unrelated children. Methods In this study, we genetically and clinically examined a 3‐year‐old proband with resolved infantile spasms and normal development. Standard whole‐exome sequencing (WES) and Sanger sequencing were performed to identify the functional impact of the variant. Results WES revealed a rare biallelic missense variant (c.3013G>C; p.Val1005Leu) in FCSK. RT‐qPCR showed a significant depletion in FCSK gene expression in the affected individual. Western blotting revealed reduced FCSK expression at the protein level compared to that in the control. Furthermore, 3D protein modeling suggested changes in the secondary structure, which might affect the overall FCSK protein function. Conclusion This study broadens the mutation and phenotypic spectrum of FCSK‐associated developmental disorders.https://doi.org/10.1002/mgg3.2117developmental delayFCSKFucokinaseFucosylationglycosylation |
| spellingShingle | Abeer Al Tuwaijri Yusra Alyafee Muhammad Umair Arwa Alsubait Mashael Alharbi Hamad AlEidi Mariam Ballow Mohammed Aldrees Qamre Alam Abdulkareem Al Abdulrahman Muhammad Talal Alrifai Majid Alfadhel Congenital disorder of glycosylation with defective fucosylation 2 (FCSK gene defect): The third report in the literature with a mild phenotype Molecular Genetics & Genomic Medicine developmental delay FCSK Fucokinase Fucosylation glycosylation |
| title | Congenital disorder of glycosylation with defective fucosylation 2 (FCSK gene defect): The third report in the literature with a mild phenotype |
| title_full | Congenital disorder of glycosylation with defective fucosylation 2 (FCSK gene defect): The third report in the literature with a mild phenotype |
| title_fullStr | Congenital disorder of glycosylation with defective fucosylation 2 (FCSK gene defect): The third report in the literature with a mild phenotype |
| title_full_unstemmed | Congenital disorder of glycosylation with defective fucosylation 2 (FCSK gene defect): The third report in the literature with a mild phenotype |
| title_short | Congenital disorder of glycosylation with defective fucosylation 2 (FCSK gene defect): The third report in the literature with a mild phenotype |
| title_sort | congenital disorder of glycosylation with defective fucosylation 2 fcsk gene defect the third report in the literature with a mild phenotype |
| topic | developmental delay FCSK Fucokinase Fucosylation glycosylation |
| url | https://doi.org/10.1002/mgg3.2117 |
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