Genotype/phenotype correlations of childhood-onset congenital sideroblastic anaemia in a European cohort

Article Article scientifique Article Genotype/phenotype correlations of childhood-onset congenital sideroblastic anaemia in a European cohort eng 2019 author Fouquet Cyrielle author Le Rouzic Marie-Amelyne author Leblanc Thierry author Fouyssac Fanny author Leverger Guy author Hessissen Laila author Marlin Sandrine author Bourrat Emmanuelle author Fahd Mony author Raffoux Emmanuel author Vannier Jean-Pierre Louis 80440 author Jäkel Nadja author Knoefler Ralf author Triolo Valerie author Pasquet Marlene author Bayart Sophie author Thuret Isabelle author Lutz Patrick author Vermylen Christiane author Touati Mohamed 671677 author Rose Christian author Matthes Thomas 27368 author Isidor Bertrand author Kannengiesser Caroline author Ducassou Stephane 530-542 10.1111/bjh.16100 31338833 0007-1048 Congenital sideroblastic anaemia (CSA) is a rare disease caused by germline mutations of genes involved in haem and iron-sulphur cluster formation, and mitochondrial protein biosynthesis. We performed a retrospective multicentre European study of a cohort of childhood-onset CSA patients to explore genotype/phenotype correlations. We studied 23 females and 20 males with symptoms of CSA. Among the patients, the most frequently mutated genes were ALAS2 (n = 10; 23·3%) and SLC25A38 (n = 8; 18·6%), causing isolated forms of microcytic anaemia of varying severity. Five patients with SLC19A2 mutations suffered from thiamine-responsive megaloblastic anaemia and three exhibited the 'anaemia, deafness and diabetes' triad. Three patients with TRNT1 mutations exhibited severe early onset microcytic anaemia associated with thrombocytosis, and two exhibited B-cell immunodeficiency, inflammatory syndrome and psychomotor delay. The prognoses of patients with TRNT1 and SLC2A38 mutations were generally dismal because of comorbidities or severe iron overload. No molecular diagnosis could be established in 14/43 cases. This study emphasizes the frequency of ALAS2 and SLC25A38 mutations and provides the largest comprehensive analysis to date of genotype/phenotype correlations in CSA. Further studies of CSA patients with data recorded in an international registry would be helpful to improve patient management and establish standardized guidelines. congenital sideroblastic anaemia genotype phenotype correlation iron overload. Dewey 616 56 Département de médecine 221 false 586 Analyses cellulaires et moléculaires des hémopathies malignes 929 British Journal of Haematology 187 4 fc6f42eb-f557-48fa-b10c-172990bebbf4 Article (Published version) Restricted bjh.16100(1).pdf 693518 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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Genotype/phenotype correlations of childhood-onset congenital sideroblastic anaemia in a European cohort	British Journal of Haematology			2019	346	3

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Touati, Mohamed