Disease risk estimates in V30M variant transthyretin amyloidosis (A-ATTRv) from Mallorca
Abstract Background Variant transthyretin amyloidosis (A-ATTRv) is an autosomal dominant disease caused by a range of TTR gene variants which entail great phenotypical heterogeneity and penetrance. In Majorca, the A-ATTRv caused by the V30M gene variant (A-ATTRV30M) is the most common. Since asympto...
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-023-02865-5 |
| _version_ | 1797451527278821376 |
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| author | E. Cisneros-Barroso F. Gorram M. A. Ribot-Sansó F. Alarcon G. Nuel J. González-Moreno A. Rodríguez J. Hernandez-Rodriguez E. Amengual-Cladera I. Martínez-López T. Ripoll-Vera I. Losada-López D. Heine-Suñer V. Plante-Bordeneuve |
| author_facet | E. Cisneros-Barroso F. Gorram M. A. Ribot-Sansó F. Alarcon G. Nuel J. González-Moreno A. Rodríguez J. Hernandez-Rodriguez E. Amengual-Cladera I. Martínez-López T. Ripoll-Vera I. Losada-López D. Heine-Suñer V. Plante-Bordeneuve |
| author_sort | E. Cisneros-Barroso |
| collection | DOAJ |
| description | Abstract Background Variant transthyretin amyloidosis (A-ATTRv) is an autosomal dominant disease caused by a range of TTR gene variants which entail great phenotypical heterogeneity and penetrance. In Majorca, the A-ATTRv caused by the V30M gene variant (A-ATTRV30M) is the most common. Since asymptomatic carriers are at risk of developing the disease, estimating age of onset is vital for proper management and follow-up. Thus, the aim of this study was to estimate age-related penetrance in ATTRV30M variant carriers from Majorca. Methods The disease risk among carriers from ATTRV30M families from Majorca was estimated by Non-parametric survival estimation. Factors potentially involved in the disease expression, namely gender and parent of origin were also analysed. Results A total of 48 heterozygous ATTRV30M families (147 affected patients and 123 were asymptomatic carriers) were included in the analysis. Penetrance progressively increased from 6% at 30 years to 75% at 90 years of age. In contrast to other European populations, we observe a similar risk for both males and females, and no difference of risk according to the parent of origin. Conclusions In this first study assessing the age-related penetrance of ATTRV30M variant in Majorcan families, no effect of gender or parent of origin was observed. These findings will be helpful for improving management and follow-up of TTR variant carrier individuals. |
| first_indexed | 2024-03-09T14:54:58Z |
| format | Article |
| id | doaj.art-3501c5edd17945e8bf02f9ed4ad5383c |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-03-09T14:54:58Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-3501c5edd17945e8bf02f9ed4ad5383c2023-11-26T14:12:44ZengBMCOrphanet Journal of Rare Diseases1750-11722023-08-011811710.1186/s13023-023-02865-5Disease risk estimates in V30M variant transthyretin amyloidosis (A-ATTRv) from MallorcaE. Cisneros-Barroso0F. Gorram1M. A. Ribot-Sansó2F. Alarcon3G. Nuel4J. González-Moreno5A. Rodríguez6J. Hernandez-Rodriguez7E. Amengual-Cladera8I. Martínez-López9T. Ripoll-Vera10I. Losada-López11D. Heine-Suñer12V. Plante-Bordeneuve13Internal Medicine Department. Fundación Instituto de Investigación Sanitaria de Las Islas Baleares, Son Llàtzer University HospitalDepartment of Neurology, University Hospital Henri MondorInternal Medicine Department. Fundación Instituto de Investigación Sanitaria de Las Islas Baleares, Son Llàtzer University HospitalLaboratory MAP5 UMR CNRS 8145, Paris UniversityStochastics and Biology Group, Department of Probability and Statistics (LPSM, UMR CNRS 8001), Sorbonne UniversityInternal Medicine Department. Fundación Instituto de Investigación Sanitaria de Las Islas Baleares, Son Llàtzer University HospitalInternal Medicine Department. Fundación Instituto de Investigación Sanitaria de Las Islas Baleares, Son Llàtzer University HospitalGenomics of Health Research Group, Health Research Institute of the Balearic Islands (IdISBa)Genomics of Health Research Group, Health Research Institute of the Balearic Islands (IdISBa)Genomics of Health Research Group, Health Research Institute of the Balearic Islands (IdISBa)Balearic Research Group in Genetic Cardiopathies, Sudden Death and TTR Amyloidosis. Health Research Institute of the Balearic Islands (IdISBa), Son Llàtzer University HospitalInternal Medicine Department. Fundación Instituto de Investigación Sanitaria de Las Islas Baleares, Son Llàtzer University HospitalGenomics of Health Research Group, Health Research Institute of the Balearic Islands (IdISBa)Department of Neurology, University Hospital Henri MondorAbstract Background Variant transthyretin amyloidosis (A-ATTRv) is an autosomal dominant disease caused by a range of TTR gene variants which entail great phenotypical heterogeneity and penetrance. In Majorca, the A-ATTRv caused by the V30M gene variant (A-ATTRV30M) is the most common. Since asymptomatic carriers are at risk of developing the disease, estimating age of onset is vital for proper management and follow-up. Thus, the aim of this study was to estimate age-related penetrance in ATTRV30M variant carriers from Majorca. Methods The disease risk among carriers from ATTRV30M families from Majorca was estimated by Non-parametric survival estimation. Factors potentially involved in the disease expression, namely gender and parent of origin were also analysed. Results A total of 48 heterozygous ATTRV30M families (147 affected patients and 123 were asymptomatic carriers) were included in the analysis. Penetrance progressively increased from 6% at 30 years to 75% at 90 years of age. In contrast to other European populations, we observe a similar risk for both males and females, and no difference of risk according to the parent of origin. Conclusions In this first study assessing the age-related penetrance of ATTRV30M variant in Majorcan families, no effect of gender or parent of origin was observed. These findings will be helpful for improving management and follow-up of TTR variant carrier individuals.https://doi.org/10.1186/s13023-023-02865-5Transthyretin amyloidosisPolyneuropathyGeneticsDisease riskGene carriers |
| spellingShingle | E. Cisneros-Barroso F. Gorram M. A. Ribot-Sansó F. Alarcon G. Nuel J. González-Moreno A. Rodríguez J. Hernandez-Rodriguez E. Amengual-Cladera I. Martínez-López T. Ripoll-Vera I. Losada-López D. Heine-Suñer V. Plante-Bordeneuve Disease risk estimates in V30M variant transthyretin amyloidosis (A-ATTRv) from Mallorca Orphanet Journal of Rare Diseases Transthyretin amyloidosis Polyneuropathy Genetics Disease risk Gene carriers |
| title | Disease risk estimates in V30M variant transthyretin amyloidosis (A-ATTRv) from Mallorca |
| title_full | Disease risk estimates in V30M variant transthyretin amyloidosis (A-ATTRv) from Mallorca |
| title_fullStr | Disease risk estimates in V30M variant transthyretin amyloidosis (A-ATTRv) from Mallorca |
| title_full_unstemmed | Disease risk estimates in V30M variant transthyretin amyloidosis (A-ATTRv) from Mallorca |
| title_short | Disease risk estimates in V30M variant transthyretin amyloidosis (A-ATTRv) from Mallorca |
| title_sort | disease risk estimates in v30m variant transthyretin amyloidosis a attrv from mallorca |
| topic | Transthyretin amyloidosis Polyneuropathy Genetics Disease risk Gene carriers |
| url | https://doi.org/10.1186/s13023-023-02865-5 |
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