Wilson Disease Prevalence
Discrepancy Between Clinical Records, Registries and Mutation Carrier Frequency
Pascual Lorente-Arencibia
Unidad de Investigación, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de GC
Search for more papers by this authorLuis García-Villarreal
Unidad de Investigación, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de GC
Search for more papers by this authorRafaela González-Montelongo
Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerif
Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, Santa Cruz de Tenerif
Search for more papers by this authorLuis A. Rubio-Rodríguez
Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerif
Search for more papers by this authorCarlos Flores
Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerif
Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, Santa Cruz de Tenerif
Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerif
CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid
Search for more papers by this authorPaloma Garay-Sánchez
Unidad de Investigación, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de GC
Search for more papers by this authorTanausú delaCruz
Unidad de Investigación, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de GC
Search for more papers by this authorMilagros Santana-Verano
Unidad de Investigación, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de GC
Search for more papers by this authorFrancisco Rodríguez-Esparragón
Unidad de Investigación, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de GC
Search for more papers by this authorJuana N. Benitez-Reyes
Department of Haematology, Complejo Hospitalario, Universitario Insular Materno-Infantil, Spain
Search for more papers by this authorFernando Fernández-Fuertes
Department of Haematology, Complejo Hospitalario, Universitario Insular Materno-Infantil, Spain
Search for more papers by this authorCorresponding Author
Antonio Tugores
Unidad de Investigación, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de GC
Address correspondence and reprint requests to Antonio Tugores, PhD, Unidad de Investigación, Complejo Hospitalario Universitario Insular Materno-Infantil, Avda Maritima del Sur s/n, 35016 Las Palmas de Gran Canaria, Spain (e-mail: [email protected]).Search for more papers by this authorPascual Lorente-Arencibia
Unidad de Investigación, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de GC
Search for more papers by this authorLuis García-Villarreal
Unidad de Investigación, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de GC
Search for more papers by this authorRafaela González-Montelongo
Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerif
Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, Santa Cruz de Tenerif
Search for more papers by this authorLuis A. Rubio-Rodríguez
Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerif
Search for more papers by this authorCarlos Flores
Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerif
Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, Santa Cruz de Tenerif
Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerif
CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid
Search for more papers by this authorPaloma Garay-Sánchez
Unidad de Investigación, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de GC
Search for more papers by this authorTanausú delaCruz
Unidad de Investigación, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de GC
Search for more papers by this authorMilagros Santana-Verano
Unidad de Investigación, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de GC
Search for more papers by this authorFrancisco Rodríguez-Esparragón
Unidad de Investigación, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de GC
Search for more papers by this authorJuana N. Benitez-Reyes
Department of Haematology, Complejo Hospitalario, Universitario Insular Materno-Infantil, Spain
Search for more papers by this authorFernando Fernández-Fuertes
Department of Haematology, Complejo Hospitalario, Universitario Insular Materno-Infantil, Spain
Search for more papers by this authorCorresponding Author
Antonio Tugores
Unidad de Investigación, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de GC
Address correspondence and reprint requests to Antonio Tugores, PhD, Unidad de Investigación, Complejo Hospitalario Universitario Insular Materno-Infantil, Avda Maritima del Sur s/n, 35016 Las Palmas de Gran Canaria, Spain (e-mail: [email protected]).Search for more papers by this authorSources of Funding: Supported by the Servicio Canario de Salud, a public non-profit health care provider, a grant from Fundación DISA to AT and grants to CF from the Ministry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER), co-financed by the ERDF “A way of making Europe” from the EU, and the Cabildo Insular de Tenerife (CGIEU0000219140).
The authors report no conflicts of interest.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org).
ABSTRACT
Objectives:
Diagnosis of Wilson disease (WD) is difficult and, as early detection may prevent all symptoms, it is essential to know the exact prevalence to evaluate the cost-efficacy of a screening program. As the number of WD patients was high in our population, we wished to estimate prevalence by determining the carrier frequency for clinically relevant ATP7B mutations.
Methods:
To estimate prevalence, screening for the most prevalent mutation was performed in 1661 individuals with ancestry in Gran Canaria, and the frequency of other mutations was estimated from patient records. Alternatively, ATP7B mutations were detected from exomes and genomes from 851 individuals with Canarian ancestry, 236 from Gran Canaria, and a public Spanish exome database.
Results:
Estimated carrier frequencies in Gran Canaria ranged from 1 in 20 to 28, depending on the method used, resulting in prevalences of 1 case per 1547 to 3140 inhabitants. Alternatively, the estimated affected frequencies were 1 in 5985 to 7980 and 1 in 6278 to 16,510 in the archipelago or mainland Spain respectively.
Conclusions:
The number of carriers predicts much higher prevalences than reported, suggesting that WD is underdiagnosed; specific mutations may remain unnoticed due to low penetrance or no signs of disease at all; regional prevalence rather than national prevalence should be considered in cost-efficacy models to approach preventive screening in the asymptomatic population and genetic screening strategies will have to deal with the genetic heterogeneity of ATP7B in the general population and in patients.
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