Inter- and Intrafamilial Clinical Variability of Fucosidosis in Cuba in the Face of Q422x Causative Mutation
Keywords:
fucosidosis, angiokeratoma, Q422X mutation.Abstract
Introduction: Fucosidosis is a rare lysosomal storage disease caused by mutations in the α-L-fucosidase gene; of these, Q422X has been found in several populations. In Cuba, patients have only been reported in Holguín province. Objective: To correlate clinical behavior with the causal mutation. Methods: A study was carried out in all families with patients diagnosed at the Provincial Center for Medical Genetics in Holguín, from 1985 to 2023. The variables studied were the presence of angiokeratoma, age of death, clinical type and causal mutation. Results: Nineteen patients were diagnosed as homozygous for Q422X mutation belonging to 13 families. 79.8% of those affected presented angiokeratoma. 43.8% died before the age of ten, 50% during the second decade of life, and only one patient after the age of 20. 42.2% had an intermediate clinical course. The age of death did not show statistically significant relationship with the presence of angiokeratoma, so the clinical types of the disease could not be precisely delimited based on these variables. Conclusions: Despite being caused solely by the Q422X mutation, fucosidosis in Holguín has behaved as a continuous clinical spectrum, with inter- and intrafamilial variability; therefore, both genetic and non-genetic factors have intervened in its phenotypic heterogeneity.Downloads
References
1. Ferreira CR, Rahman S, Keller M, Zschocke J. An International Classification of Inherited Metabolic Disorders (ICIMD). J Inherit Metab Dis. 2021 [acceso 10/03/2023];44(1):164-77. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021760/
2. Mao SJ, Zhao J, Shen Z, Zou CC. An unusual presentation of fucosidosis in a Chinese boy: a case report and literature review (childhood fucosidosis). BMC Pediatr. 2022 [acceso 15/03/2023];22(1). Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277805
3. Willems PJ, Gatti R, Darby JK, Romeo G, Durand P, Dumon JE, et al. Fucosidosis revisited: a review of 77 patients. Am J Med Genet. 1991 [acceso 01/03/2023];38(1):111-31. Disponible en: https://pubmed.ncbi.nlm.nih.gov/2012122
4. Stepien KM, Ciara E, Jezela-Stanek A. Fucosidosis-Clinical Manifestation, Long-Term Outcomes, and Genetic Profile-Review and Case Series. Genes (Basel). 2020 [acceso 15/03/2023];11(11). Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700486
5. Kulcsarova K, Baloghova J, Necpal J, Skorvanek M. Skin conditions and movement disorders: hiding in plain sight. Mov Disord Clin Pract. 2022 [acceso 15/08/2023];9(5) Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274368
6. Zhang X, Zhao S, Liu H, Wang X, Wang X, Du N, et al. Identification of a novel homozygous loss-of-function mutation in FUCA1 gene causing severe Fucosidosis: A case report. J Int Med Res. 2021 [acceso 12/03/2023];49(4). Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111281
7. Domin A, Zabek T, Kwiatkowska A, Szmatola T, Deregowska A, Lewinska A, et al. The Identification of a Novel Fucosidosis-Associated FUCA1 Mutation: A Case of a 5-Year-Old Polish Girl with Two Additional Rare Chromosomal Aberrations and Affected DNA Methylation Patterns. Genes (Basel). 2021 [acceso 01/03/2023];12(1). Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC7827884
8. Do Rosario MC, Purushothama G, Narayanan DL, Siddiqui S, Girisha KM, Shukla A. Extended analysis of exome sequencing data reveals a novel homozygous deletion of exons 3 and 4 in FUCA1 gene causing Fucosidosis in an Indian family. Clin Dysmorphol. 2023 [acceso 10/12/2023];28. Disponible en: https://pubmed.ncbi.nlm.nih.gov/36876340
9. Gowda VK, Srinivasan VM, Vegda H, Bhat M. Fucosidosis with Pathogenic Variant in FUCA1 Gene. Indian J Pediatr. 2020 [acceso 10/03/2023];87(10):867-8. Disponible en: https://pubmed.ncbi.nlm.nih.gov/32125660
10. Bhattacherjee A, Desa E, Ahmad Lone K, Jaiswal A, Tyagi S, Dalal A. Genotype first approach & familial segregation analysis help in the elucidation of disease-causing variant for Fucosidosis. Indian J Med Res. 2023 [acceso 08/10/23];157:363-6. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC10438398
11. El-Amawy HS, Dawoud H. Lysosomal storage diseases in the era of COVID-19: a report of an Egyptian case of alpha-fucosidosis and a summary of the lysosomal storage diseases-COVID-19 relationship. Egypt J Med Hum Genet. 2022 [acceso 08/10/23];23(1). Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9483389
12. Abozaid GM, Kerr K, McKnight A, Al-Omar HA. Criteria to define rare diseases and orphan drugs: a systematic review protocol. BMJ Open. 2022 [acceso 18/4/23];12(7). Disponible en: https://pubmed.ncbi.nlm.nih.gov/ 35906057
13. Wang L, Yang M, Hong S, Tang T, Zhuang J, Huang H. Fucosidosis in a Chinese boy: a case report and literature review. J Int Med Res. 2020 [acceso 18/4/23];48(4). Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132800
14. Chkioua L, Amri Y, Chaima S, Fenni F, Boudabous H, Ben Turkia H, et al. Fucosidosis in Tunisian patients: mutational analysis and homology-based modeling of FUCA1 enzyme. BMC Med Genomics. 2021 [acceso 08/10/23];14(1). Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383439
15. Turkia HB, Tebib N, Azzouz H, Abdelmoula MS, Bouguila J, Sanhaji H, et al. Phenotypic spectrum of fucosidosis in Tunisia. J Inherit Metab Dis. 2008 [acceso 07/10/23];31(2):313-6. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771954
16. Tamayo-Chang VJ, Llauradó-Robles RA, Campos-Hernández D, Monaga-Castillo M, Santana-Hernández EE. Fucosidosis en la Provincia Holguín. Causas y frecuencia. Rev Cubana Genet Comunit. 2013 [acceso 07/10/23];7(2):33-7. Disponible en: https://www.medigraphic.com/pdfs/revcubgencom/cgc-2013/cgc132f.pdf
17. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 [acceso 07/10/23];16(3):1215-8. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC334765
18. Kretz KA, Darby J K, Willems PJ, O’Brien JS. Characterization of EcoRI mutation in Fucosidosis patients: A stop codon in the open reading frame. J Mol Neurosci. 1989 [acceso 07/10/21];1:177-80. Disponible en: https://link.springer.com/article/10.1007/BF02918904#authJohn_S_O_Brien
19. Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, et al. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 [acceso 07/10/21];239(4839):487-91. Disponible en: https://pubmed.ncbi.nlm.nih.gov/2448875
20. World Medical Association. Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013 [acceso 07/10/21];310(20):2191-4. Disponible en: https://pubmed.ncbi.nlm.nih.gov/24141714
21. Willems PJ, Garcia CA, De Smedt MC, Martin-Jimenez R, Darby JK, Duenas DA, et al. Intrafamilial variability in Fucosidosis. Clin Genet. 1988 [acceso 07/10/21];34(1):7-14. Disponible en: https://pubmed.ncbi.nlm.nih.gov/3409541
22. Puente-Ruiz N, Ellis I, Bregu M, Chen C, Church HJ, Tylee KL, et al. Long-term outcomes in two adult siblings with Fucosidosis-Diagnostic odyssey and clinical manifestations. Mol Genet Metab Rep. 2023 [acceso 07/10/21];37. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694746
23. Ficicioglu C, Giugliani R, Harmatz P, Mendelsohn NJ, Jego V, Parini R. Intrafamilial variability in the clinical manifestations of mucopolysaccharidosis type II: Data from the Hunter Outcome Survey (HOS). Am J Med Genet A. 2018 [acceso 07/10/21];176(2):301-10. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814921
24. Mkaouar R, Riahi Z, Charfeddine C, Chelly I, Boudabbous H, Dallali H. Alpha-mannosidosis in Tunisian consanguineous families: Potential involvement of variants in GHR and SLC19A3 genes in the variable expressivity of cognitive impairment. PLoS One. 2021 [acceso 08/10/23];16(10). Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494324
25. Reith M, Zeltner L, Schäferhoff K, Witt D, Zuleger T, Haack TB. A Novel, Apparently Silent Variant in MFSD8 Causes Neuronal Ceroid Lipofuscinosis with Marked Intrafamilial Variability. Int J Mol Sci. 2022 [acceso 08/10/23];23(4). Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877174
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