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Familial hypercholesterolaemia in Portugal

  • M. Bourbon
    Correspondence
    Corresponding author at: Unid. Investigação Cardiovascular, Inst. Nacional de Saúde, Lisbon, Portugal. Tel.: +351 217 526 476; fax: +351 217 526 400.
    Affiliations
    Unid. Investigação Cardiovascular, Inst. Nacional de Saúde, Lisbon, Portugal

    MRC Lipoprotein Group, Clinical Sciences Centre, Hammersmith Hospital, London, UK
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  • A.C. Alves
    Affiliations
    Unid. Investigação Cardiovascular, Inst. Nacional de Saúde, Lisbon, Portugal
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  • A.M. Medeiros
    Affiliations
    Unid. Investigação Cardiovascular, Inst. Nacional de Saúde, Lisbon, Portugal
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  • S. Silva
    Affiliations
    Unid. Investigação Cardiovascular, Inst. Nacional de Saúde, Lisbon, Portugal
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  • A.K. Soutar
    Affiliations
    MRC Lipoprotein Group, Clinical Sciences Centre, Hammersmith Hospital, London, UK
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  • on behalf of the investigators of the Portuguese FH study
    Author Footnotes
    1 “The Portuguese Familial Hypercholesterolaemia Study” is being developed at the Unidade de Investigação Cardiovascular, Centro de Biopatologia, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA). Coordinator: Dr. Mafalda Bourbon. Clinical consultant: Dr. Quitéria Rato. Molecular research: Dr. Mafalda Bourbon (principal investigator), Ana Catarina Alves, Ana Margarida Medeiros and Sónia Silva, Unidade de Investigação Cardiovascular, CBP, INSA. Clinical reseach: Prof. António Guerra, Serv. de Pediatria, Hosp. de S. João, E.P.E., Porto; Dr. António Furtado, Serv. de Med. Interna, Hosp. Pedro Hispano, Matosinhos; Prof. José Manuel Silva, Serv. de Med. Interna, HUC, Coimbra; Dr. António Cruz, Serv. Pediatria, Hosp. Sto André, Leiria; Dr. Lina Cardoso Ramos, Serv. Genética, Dr. Paula Garcia, Unid. Doenças Metabólicas, Hosp. Pediátrico, Coimbra; Dr. Isabel Gaspar, Serv. de Genética, Dr. Ana Gaspar, Serv Pediatria, Hosp. de Santa Maria, E.P.E., Lisboa; Prof. Graça Morais, Dept. de Bioquímica, Fac. de Ciências Médicas, UNL, Lisboa; Prof. Heloísa Santos, Fundação Professor Fernando de Pádua, Lisboa; Dr. Pedro Marques da Silva, Serv. de Med. Interna, Hosp. de Santa Marta, E.P.E, Lisboa; Dr. João Sequeira Duarte, Serv. de Endocrinologia, Hosp. de Egas Moniz, Lisboa; Dr. Leonor Sassetti, Unid. de Adolescentes, Dr. Sílvia Sequeira, Serv. Doenças Metabólicas, Hosp. D. Estefânia, Lisboa; Dr. Piedade Sande Lemos, Serv Pediatria, Hosp Amadora Sintra, Amadora; Dr. Renata Rossi, Serv. Cardiologia Pediátrica, Dr. Margarida Bruges Serv Nefrologia, Hosp. Sta. Cruz, Carnaxide; Dr. Mário Amaro, Serv Medicina Interna, Hospital Garcia da Orta, Almada; Dr. Quitéria Rato, Serv. de Cardiologia, CHS, Hosp. de São Bernardo, Setúbal; Dr. Mª Luísa Gonçalves, Serv. Medicina Interna, Hosp. Litoral Alentejano, Santiago do Cacém; Dr. Isabel Azevedo, Serv. de Med. Interna I, Hosp. dos Marmeleiros, Funchal.
  • Author Footnotes
    1 “The Portuguese Familial Hypercholesterolaemia Study” is being developed at the Unidade de Investigação Cardiovascular, Centro de Biopatologia, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA). Coordinator: Dr. Mafalda Bourbon. Clinical consultant: Dr. Quitéria Rato. Molecular research: Dr. Mafalda Bourbon (principal investigator), Ana Catarina Alves, Ana Margarida Medeiros and Sónia Silva, Unidade de Investigação Cardiovascular, CBP, INSA. Clinical reseach: Prof. António Guerra, Serv. de Pediatria, Hosp. de S. João, E.P.E., Porto; Dr. António Furtado, Serv. de Med. Interna, Hosp. Pedro Hispano, Matosinhos; Prof. José Manuel Silva, Serv. de Med. Interna, HUC, Coimbra; Dr. António Cruz, Serv. Pediatria, Hosp. Sto André, Leiria; Dr. Lina Cardoso Ramos, Serv. Genética, Dr. Paula Garcia, Unid. Doenças Metabólicas, Hosp. Pediátrico, Coimbra; Dr. Isabel Gaspar, Serv. de Genética, Dr. Ana Gaspar, Serv Pediatria, Hosp. de Santa Maria, E.P.E., Lisboa; Prof. Graça Morais, Dept. de Bioquímica, Fac. de Ciências Médicas, UNL, Lisboa; Prof. Heloísa Santos, Fundação Professor Fernando de Pádua, Lisboa; Dr. Pedro Marques da Silva, Serv. de Med. Interna, Hosp. de Santa Marta, E.P.E, Lisboa; Dr. João Sequeira Duarte, Serv. de Endocrinologia, Hosp. de Egas Moniz, Lisboa; Dr. Leonor Sassetti, Unid. de Adolescentes, Dr. Sílvia Sequeira, Serv. Doenças Metabólicas, Hosp. D. Estefânia, Lisboa; Dr. Piedade Sande Lemos, Serv Pediatria, Hosp Amadora Sintra, Amadora; Dr. Renata Rossi, Serv. Cardiologia Pediátrica, Dr. Margarida Bruges Serv Nefrologia, Hosp. Sta. Cruz, Carnaxide; Dr. Mário Amaro, Serv Medicina Interna, Hospital Garcia da Orta, Almada; Dr. Quitéria Rato, Serv. de Cardiologia, CHS, Hosp. de São Bernardo, Setúbal; Dr. Mª Luísa Gonçalves, Serv. Medicina Interna, Hosp. Litoral Alentejano, Santiago do Cacém; Dr. Isabel Azevedo, Serv. de Med. Interna I, Hosp. dos Marmeleiros, Funchal.

      Abstract

      Familial hypercholesterolaemia (FH) is characterised clinically by an increased level of circulating LDL cholesterol that leads to lipid accumulation in tendons and arteries, premature atherosclerosis and increased risk of coronary heart disease (CHD). Although Portugal should have about 20,000 cases, this disease is severely under-diagnosed in our country, this being the first presentation of Portuguese data on FH. A total of 602 blood samples were collected from 184 index patients and 418 relatives from several centres throughout Portugal. Fifty-three different mutations were found in 83 index patients, 79 heterozygous and 4 with two defective LDLR alleles. Additionally, 4 putative alterations were found in 8 patients but were not considered mutations causing disease, mainly because they did not co-segregate with hypercholesterolaemia in the families. Three unrelated patients were found to be heterozygous for the APOB3500 mutation and two unrelated patients were found to be heterozygous for a novel mutation in PCSK9, predicted to cause a single amino acid substitution, D374H. Cascade screening increased the number of FH patients identified genetically to 204. The newly identified FH patients are now receiving counselling and treatment based on the genetic diagnosis. The early identification of FH patients can increase their life expectancy and quality of life by preventing the development of premature CHD if patients receive appropriate pharmacological treatment.

      Keywords

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