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Analysis of a cohort of 101 CDAII patients: description of 24 new molecular variants and genotype‐phenotype correlations
Author(s) -
Bianchi Paola,
Schwarz Klaus,
Högel Josef,
Fermo Elisa,
Vercellati Cristina,
Grosse Regine,
Wijk Richard,
Zwieten Rob,
Barcellini Wilma,
Zanella Alberto,
Heimpel Hermann
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14271
Subject(s) - missense mutation , genotype , haemolysis , phenotype , biology , genotype phenotype distinction , genetics , mutation , erythroblast , gene , ineffective erythropoiesis , erythropoiesis , immunology , medicine , anemia , stem cell , haematopoiesis
Summary Congenital dyserythropoietic anaemia type II ( CDAII ) is a rare autosomal recessive disease characterized by ineffective erythropoiesis, haemolysis, erythroblast morphological abnormalities, hypoglycosylation of some red blood cell membrane proteins, particularly band 3, and mutations in the SEC 23B gene. We report the analysis of 101 patients from 91 families with a median follow‐up of 23 years (range 0–65); 68 patients are newly reported. Clinical and haematological parameters were separately analysed in early infancy and thereafter, when feasible. Molecular analysis of the SEC 23B gene confirmed the high heterogeneity of the defect, leading to the identification of 54 different mutations, 24 of which are newly described. To evaluate the genotype‐phenotype correlation, patients were grouped according to their genotype (two missense mutations vs. one missense/one drastic mutation) and assigned to two different severity gradings based on laboratory data and on therapeutic needs; by this approach only a weak genotype‐phenotype correlation was observed in the analysed groups.