FBXW7 neurodevelopmental syndrome
| FBXW7 neurodevelopmental syndrome | |
|---|---|
| Other names: FBXW7 neurodevelopmental disorder | |
 | |
| a-c)Illustration of SCFFBXW7 E3 ubiquitin ligase complex and FBXW7 gene and proteins | |
 | |
| Specialty | Medical genetics, Neurology |
| Symptoms | Multi-systemic |
| Complications | Social skill issues, constant uncomfortability, muscle problems |
| Usual onset | Birth |
| Duration | Lifelong |
| Causes | Genetic mutation in the FBXW7 gene, in chromosome 4q |
| Prognosis | Good (with treatment) |
| Frequency | 35 cases have been reported in medical literature |
FBXW7 neurodevelopmental syndrome is a genetic disorder which is characterized by gastrointestinal, brain, and muscle anomalies accompanied by intellectual disabilities and developmental delays.
The condition was first described in 2022.
Signs and symptoms
A study done found individuals with this condition had intellectual disabilities and developmental delays that ranged from borderline to severe, 62% of FBXW7 patients had hypotonia, 46% had feeding difficulties and regular constipation, and 23% of them had epilepsy. Brain imaging revealed anomalies in the structure of the cerebellum, the nervous fibres, and in the brain's white matter. Reduction of the gene associated with this condition in a fly model resulted in an intellectually impaired fly which didn't fly away when exposed to stimulus.[1]
Causes
This condition is associated with either nonsense/frameshift/splice-site/missense mutations or heterozygous deletions of the tumor suppressor FBXW7 gene, in chromosome 4.[2] These mutations (most commonly the missense ones) were concentrated in the substrate binding surface of the WD40 domain, they (the mutations) are thought to reduce substrate binding balance.[3]
Epidemiology
This condition has been described in 35 individuals from 32 families in 7 countries worldwide.[4]
The age of these people ranged from 2 years old to 44 years[5] old.
History
This condition was first discovered in April 2022 by Sarah E M Stephenson et al., they gathered 35 people from across the world and analyzed their genome. It had its fair share of media coverage, being reported on medical websites from India, Australia, and the U.S., among many more.[6]
References
- ↑ "Researchers discover new neurodevelopmental disorder". ScienceDaily. Archived from the original on 2022-05-17. Retrieved 2022-06-21.
- ↑ Yeh, Chien-Hung; Bellon, Marcia; Nicot, Christophe (2018-08-07). "FBXW7: a critical tumor suppressor of human cancers". Molecular Cancer. 17 (1): 115. doi:10.1186/s12943-018-0857-2. ISSN 1476-4598. PMC 6081812. PMID 30086763.
- ↑ Stephenson, Sarah E. M.; Costain, Gregory; Blok, Laura E. R.; Silk, Michael A.; Nguyen, Thanh Binh; Dong, Xiaomin; Alhuzaimi, Dana E.; Dowling, James J.; Walker, Susan; Amburgey, Kimberly; Hayeems, Robin Z. (2022-04-07). "Germline variants in tumor suppressor FBXW7 lead to impaired ubiquitination and a neurodevelopmental syndrome". American Journal of Human Genetics. 109 (4): 601–617. doi:10.1016/j.ajhg.2022.03.002. ISSN 1537-6605. PMC 9069070. PMID 35395208.
- ↑ "New neurodevelopmental disorder identified". www.labonline.com.au. Retrieved 2022-06-21.
{{cite web}}: CS1 maint: url-status (link) - ↑ April 8, Karishma Abhishek on; AM, 2022 at 12:05 (8 April 2022). "Discovery of New Neurodevelopmental Syndrome Linked to Tumor-specific Genes". Medindia. Archived from the original on 2022-05-04. Retrieved 2022-06-21.
- ↑ "Redirecting". linkinghub.elsevier.com. Archived from the original on 2023-10-22. Retrieved 2022-06-21.