title: Analysis of a cohort of 101 CDAII patients: description of 24 new molecular variants and genotype-phenotype correlations.
abstract: 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 SEC23B 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 SEC23B 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.
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, UO Oncoematologia, UOS Fisiopatologia delle Anemie, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bianchi
authors.affiliation: Institute for Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Service Baden-Wuerttemberg - Hessen and Institute for Transfusion Medicine, University of Ulm, Ulm, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schwarz
authors.affiliation: Institute for Human Genetics, University Ulm, Ulm, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Högel
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, UO Oncoematologia, UOS Fisiopatologia delle Anemie, Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Fermo
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, UO Oncoematologia, UOS Fisiopatologia delle Anemie, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Vercellati
authors.affiliation: Klinik für Pädiatrische Hämatologie und Onkologie, Universität Hamburg, Hamburg, Germany.
authors.forename: Regine
authors.initials: R
authors.lastname: Grosse
authors.affiliation: University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Richard
authors.initials: R
authors.lastname: van Wijk
authors.affiliation: Laboratory of Red Blood Cell Diagnostics, Department of Blood Cell Research, Sanquin Blood Supply Foundation, Amsterdam, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: van Zwieten
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, UO Oncoematologia, UOS Fisiopatologia delle Anemie, Milan, Italy.
authors.forename: Wilma
authors.initials: W
authors.lastname: Barcellini
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, UO Oncoematologia, UOS Fisiopatologia delle Anemie, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zanella
authors.affiliation: Department Internal Medicine III, University Hospital Ulm, Ulm, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Heimpel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000742:Anemia, Dyserythropoietic, Congenital / Q000175:diagnosis* / Q000235:genetics*; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006403:Hematologic Tests; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: 
  CDAII
  ; anaemia; congenital dyserythropoietic anaemia type II; genotype/phenotype; red cell