Mosaic variegated aneuploidy syndrome

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Mosaic variegated aneuploidy syndrome
Other namesMVA, Warburton-Anyane-Yeboa syndrome
Person with VMA shows facial signs and aneuploidy.svg
Photo of person and their karyotype, showing facial feeatures (High forehead, midface hypoplasia, long philtrum, hypertelorism, epicanthal folds, short and wide nose, depressed nasal bridge). Karyotype shows trisomy of chromsome 17 and chromosome 8.
Specialty Medical genetics
Symptoms Peritoneal fluid excess, cataracts, Dandy-Walker malformation, epicanthus, glaucoma, small jaw, increased nuchal translucency, short stature, enlargement of ventricles in the brain
Causes genetic mutations
Frequency1 per 1,000,000

Mosaic variegated aneuploidy syndrome is a rare autosomal recessive genetic disorder that causes inappropriate chromosomal segregation in mitosis process and because of it, some cells are aneuploid (mosaic). [1] It is caused by mutation BUB1 , BUB1B , BUB3 , CEP57 or TRIP13 . [2] [3] [4] [5]

Contents

Person with MVA can present with IUGR, microcephaly and a wide range of congenital abnormalities. [6]

Symptoms

Signs of this disease are: [7]

Very frequent:

Frequent:

Occasional:

Cause

This disorder is caused by defect of genes that are responsible for spindle checkpoint. [8]

Types include:

Genes that can cause MVA
TypeOMIMGeneLocus
MVA1 257300 BUB1B 15q15.1
MVA2 614114 CEP57 11q21
MVA3 617598 TRIP13 5p15
MVA4 620153 CENATAC 11q23
MVA5 620184 SLF2 10q24
MVA6 620185 SMC5 9q21

Also those genes are associated with that disorder: BUB3 and BUB1. [9]

Pathophysiology

BUB1, BUB1B and BUB3 participates in spindle checkpoint checkpoint process which is necessary for correct chromosome splitting process in mitosis, consequently mutation of those 3 genes causes incorrect splitting of chromosomes. [10] [11]

CENATAC gene is responsible for minor (U12‐dependent) spliceosome, which is important for cell cycle regulation proteins and in MVA, this process is deregulated. [12]

CEP57 plays role in spindle pole integrity, which mutation can cause incorrect segregation during mitosis. [13] [14]

SLF2 and SMC5 are necessary for proper chromosomal segregation through centromeric and sister chromatid cohesion, consequently this mechanism is disrupted in this disease. [15]

TRIP13 also participates in spindle checkpoint process by activating MAD2 and that activates spindle checkpoint and mutations in TRIP13 can cause MVA . [16]

Diagnosis

MVA can be suspected by phenotype and confirmed by 1.karyotyping, and 2.genetic testing. [17] [18]

  1. Karyotyping is a process, when person's chromosomes are getting isolated and ordered in numerical order, consequently it can be checked for any anomalies. [19]
  2. Genetic testing is a process when person's blood or other tissue gets inspected to determine changes in their genes. [20]

Prognosis

The prognosis of MVA syndrome depends on the types of malformation presented in the individual. [21]

History

The first mention of MVA was made by Rudd and colleagues in 1983, although Warburton and colleagues coined the name of MVA in 1991. [22] [23]

Prevalence

The prevalence of that disorder is 1/1 000 000. [17]

References

  1. ↑ "Orphanet: Diseases". www.orpha.net. Retrieved 2025-03-21.
  2. ↑ "Entry - #257300 - MOSAIC VARIEGATED ANEUPLOIDY SYNDROME 1; MVA1 - OMIM". omim.org. Retrieved 2025-03-21.
  3. ↑ "Entry - *607951 - CENTROSOMAL PROTEIN, 57-KD; CEP57 - OMIM". omim.org. Retrieved 2025-03-21.
  4. ↑ "Entry - #617598 - MOSAIC VARIEGATED ANEUPLOIDY SYNDROME 3; MVA3 - OMIM". omim.org. Retrieved 2025-03-21.
  5. ↑ "Mosaic variegated aneuploidy syndrome 1 (Concept Id: C1850343) - MedGen - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-03-21.
  6. ↑ García-Castillo, Herbert; Vásquez-Velásquez, Ana Isabel; Rivera, Horacio; Barros-Núñez, Patricio (2008). "Clinical and genetic heterogeneity in patients with mosaic variegated aneuploidy: Delineation of clinical subtypes" . American Journal of Medical Genetics Part A. 146A (13): 1687–1695. doi:10.1002/ajmg.a.32315. ISSN   1552-4833. PMID   18548531.
  7. ↑ "Orphanet: Clinical signs and symptoms". www.orpha.net. Retrieved 2025-03-21.
  8. ↑ Matsuura, Shinya; Ito, Emi; Tauchi, Hiroshi; Komatsu, Kenshi; Ikeuchi, Tatsuro; Kajii, Tadashi (2000-08-01). "Chromosomal Instability Syndrome of Total Premature Chromatid Separation with Mosaic Variegated Aneuploidy Is Defective in Mitotic-Spindle Checkpoint". The American Journal of Human Genetics. 67 (2): 483–486. doi:10.1086/303022. ISSN   0002-9297. PMC   1287192 . PMID   10877982.
  9. ↑ Voer, Richarda M. de; Kessel, Ad Geurts van; Weren, Robbert D. A.; Ligtenberg, Marjolijn J. L.; Smeets, Dominique; Fu, Lei; Vreede, Lilian; Kamping, Eveline J.; Verwiel, Eugène T. P.; Hahn, Marc-Manuel; Ariaans, Maayke; Spruijt, Liesbeth; Essen, Ton van; Houge, Gunnar; Schackert, Hans K. (2013-09-01). "Germline Mutations in the Spindle Assembly Checkpoint Genes BUB1 and BUB3 Are Risk Factors for Colorectal Cancer". Gastroenterology. 145 (3): 544–547. doi:10.1053/j.gastro.2013.06.001. ISSN   0016-5085. PMID   23747338.
  10. ↑ Bolanos-Garcia, Victor M.; Blundell, Tom L. (2011-03-01). "BUB1 and BUBR1: multifaceted kinases of the cell cycle". Trends in Biochemical Sciences. 36 (3): 141–150. doi:10.1016/j.tibs.2010.08.004. ISSN   0968-0004. PMC   3061984 . PMID   20888775.
  11. ↑ Taylor, S. S.; Ha, E.; McKeon, F. (1998-07-13). "The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase". The Journal of Cell Biology. 142 (1): 1–11. doi:10.1083/jcb.142.1.1. ISSN   0021-9525. PMC   2133037 . PMID   9660858.
  12. ↑ de Wolf, Bas; Oghabian, Ali; Akinyi, Maureen V; Hanks, Sandra; Tromer, Eelco C; van Hooff, Jolien J E; van Voorthuijsen, Lisa; van Rooijen, Laura E; Verbeeren, Jens; Uijttewaal, Esther C H; Baltissen, Marijke P A; Yost, Shawn; Piloquet, Philippe; Vermeulen, Michiel; Snel, Berend (2021-07-15). "Chromosomal instability by mutations in the novel minor spliceosome component CENATAC". The EMBO Journal. 40 (14) e106536. doi:10.15252/embj.2020106536. ISSN   0261-4189. PMC   8280824 . PMID   34009673.
  13. ↑ Snape, Katie; Hanks, Sandra; Ruark, Elise; Barros-Núñez, Patricio; Elliott, Anna; Murray, Anne; Lane, Andrew H.; Shannon, Nora; Callier, Patrick; Chitayat, David; Clayton-Smith, Jill; FitzPatrick, David R.; Gisselsson, David; Jacquemont, Sebastien; Asakura-Hay, Keiko (June 2011). "Mutations in CEP57 cause mosaic variegated aneuploidy syndrome". Nature Genetics. 43 (6): 527–529. doi:10.1038/ng.822. ISSN   1546-1718. PMC   3508359 . PMID   21552266.
  14. ↑ Wu, Qixi; He, Runsheng; Zhou, Haining; Yu, Albert CH; Zhang, Bo; Teng, Junlin; Chen, Jianguo (September 2012). "Cep57, a NEDD1-binding pericentriolar material component, is essential for spindle pole integrity". Cell Research. 22 (9): 1390–1401. doi:10.1038/cr.2012.61. ISSN   1748-7838. PMC   3434346 . PMID   22508265.
  15. ↑ Grange, Laura J.; Reynolds, John J.; Ullah, Farid; Isidor, Bertrand; Shearer, Robert F.; Latypova, Xenia; Baxley, Ryan M.; Oliver, Antony W.; Ganesh, Anil; Cooke, Sophie L.; Jhujh, Satpal S.; McNee, Gavin S.; Hollingworth, Robert; Higgs, Martin R.; Natsume, Toyoaki (2022-11-04). "Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy". Nature Communications. 13 (1): 6664. Bibcode:2022NatCo..13.6664G. doi:10.1038/s41467-022-34349-8. ISSN   2041-1723. PMC   9636423 . PMID   36333305.
  16. ↑ Kim, Dong Hyun; Han, Joo Seok; Ly, Peter; Ye, Qiaozhen; McMahon, Moira A.; Myung, Kyungjae; Corbett, Kevin D.; Cleveland, Don W. (2018-10-19). "TRIP13 and APC15 drive mitotic exit by turnover of interphase- and unattached kinetochore-produced MCC". Nature Communications. 9 (1): 4354. Bibcode:2018NatCo...9.4354K. doi:10.1038/s41467-018-06774-1. ISSN   2041-1723. PMC   6195577 . PMID   30341343.
  17. 1 2 Yamaguchi, Tomoko; Yamaguchi, Masatoshi; Akeno, Keiko; Fujisaki, Midori; Sumiyoshi, Kaeko; Ohashi, Masanao; Sameshima, Hiroshi; Ozaki, Mamoru; Kato, Maki; Kato, Takema; Hosoba, Eriko; Kurahashi, Hiroki (2018). "Prenatal diagnosis of premature chromatid separation/mosaic variegated aneuploidy (PCS/MVA) syndrome" . Journal of Obstetrics and Gynaecology Research. 44 (7): 1313–1317. doi:10.1111/jog.13647. ISSN   1447-0756. PMID   29673003.
  18. ↑ Feng, Biyun; Chang, Guoying; Zhang, Qianwen; Li, Xin; Tang, Yijun; Gu, Shili; Wang, Yirou; Wang, Jian; Wang, Xiumin (2022). "A novel CEP57 variant associated with mosaic variegated aneuploidy syndrome in a Chinese female presenting with short stature, microcephaly, brachydactyly, and small teeth". Molecular Genetics & Genomic Medicine. 10 (6) e1951. doi:10.1002/mgg3.1951. ISSN   2324-9269. PMC   9184657 . PMID   35434947.
  19. ↑ "Karyotype". www.genome.gov. Retrieved 2025-03-29.
  20. ↑ Alliance, Genetic; Screening Services, The New York-Mid-Atlantic Consortium for Genetic and Newborn (2009-07-08), "GENETIC TESTING", Understanding Genetics: A New York, Mid-Atlantic Guide for Patients and Health Professionals, Genetic Alliance, retrieved 2025-03-29
  21. ↑ "Mosaic variegated aneuploidy syndrome". atlasgeneticsoncology.org. Retrieved 2025-03-22.
  22. ↑ Rudd, Noreen L.; Teshima, Iluko E.; Martin, Renee H.; Sisken, Jesse E.; Weksberg, Rosanna (1983-12-01). "A dominantly inherited cytogenetic anomaly: A possible cell division mutant" . Human Genetics. 65 (2): 117–121. doi:10.1007/BF00286646. ISSN   1432-1203. PMID   6654324.
  23. ↑ Warburton, D.; Anyane-Yeboa, K.; Taterka, P.; Yu, C. Y.; Olsen, D. (1991). "Mosaic variegated aneuploidy with microcephaly: a new human mitotic mutant?". Annales de Génétique. 34 (3–4): 287–292. ISSN   0003-3995. PMID   1809239.
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