Clinical and haematological consequences of recurrent G6PD mutations and a single new mutation causing chronic nonspherocytic haemolytic anaemia
Tom J. Vulliamy
Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, U.K.,
Search for more papers by this authorJaspal S. Kaeda
Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, U.K.,
Search for more papers by this authorDahlila Ait-Chafa
Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, U.K.,
Search for more papers by this authorRosa Mangerini
Dipartimento di Oncologia Clinica e Sperimentale, Universitá di Genova and Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy,
Search for more papers by this authorDavid Roper
Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, U.K.,
Search for more papers by this authorJose Barbot
Minesterio da Saude, Hospital Central Especializado de Criancas Maria Pia, Porto, Portugal,
Search for more papers by this authorAthul B. Mehta
Department of Haematology, Royal Free Hospital, London, U.K.,
Search for more papers by this authorAthanassiou-Metaxa
First Paediatric Clinic, University of Thessaloniki, Greece,
Search for more papers by this authorLucio Luzzatto
Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, U.S.A.
Search for more papers by this authorPhilip J. Mason
Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, U.K.,
Search for more papers by this authorTom J. Vulliamy
Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, U.K.,
Search for more papers by this authorJaspal S. Kaeda
Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, U.K.,
Search for more papers by this authorDahlila Ait-Chafa
Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, U.K.,
Search for more papers by this authorRosa Mangerini
Dipartimento di Oncologia Clinica e Sperimentale, Universitá di Genova and Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy,
Search for more papers by this authorDavid Roper
Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, U.K.,
Search for more papers by this authorJose Barbot
Minesterio da Saude, Hospital Central Especializado de Criancas Maria Pia, Porto, Portugal,
Search for more papers by this authorAthul B. Mehta
Department of Haematology, Royal Free Hospital, London, U.K.,
Search for more papers by this authorAthanassiou-Metaxa
First Paediatric Clinic, University of Thessaloniki, Greece,
Search for more papers by this authorLucio Luzzatto
Department of Human Genetics, Memorial Sloan-Kettering Cancer Center, New York, U.S.A.
Search for more papers by this authorPhilip J. Mason
Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, U.K.,
Search for more papers by this authorAbstract
We have determined the causative mutation in 12 cases of glucose-6-phosphate dehydrogenase deficiency associated with chronic non-spherocytic haemolytic anaemia. In 11 of them the mutation we found had been previously reported in unrelated individuals. These mutations comprise seven different missense mutations and a 24 base pair deletion, G6PD Nara, previously found in a Japanese boy. Repeated findings of the same mutations suggests that a limited number of amino acid changes can produce the CNSHA phenotype and be compatible with normal development. The one new mutation we have found, G6PD Serres, is 1082 C → T causing a 361 Ala → Val substitution in the dimer interface where most other severe G6PD mutations are found. Now that several patients with the same mutation have been reported we can compare the resulting clinical phenotypes. For each mutation we find a reasonably consistent clinical picture, ranging from mild (G6PD Clinic) through moderate (G6PD Nashville) to severe (G6PD Beverly Hills and G6PD Nara).
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