Molecular analysis of 42 patients with congenital dyserythropoietic anemia type II: new mutations in the SEC23B gene and a search for a genotype-phenotype relationship

被引:48
作者
Iolascon, Achille [1 ,2 ]
Russo, Roberta [1 ,2 ]
Esposito, Maria Rosaria [1 ,2 ]
Asci, Roberta [1 ]
Piscopo, Carmelo [1 ,2 ]
Perrotta, Silverio [3 ]
Feneant-Thibault, Madeleine [4 ]
Garcon, Loic [5 ]
Delaunay, Jean [6 ]
机构
[1] CEINGE Biotecnol Avanzate, Naples, Italy
[2] Univ Naples Federico 2, Dept Biochem & Med Biotechnol, Naples, Italy
[3] Univ Naples 2, Dept Pediat, Naples, Italy
[4] Hop Bicetre, Serv Biochim, Le Kremlin Bicetre, France
[5] Hop Hotel Dieu, Serv Hematol Gen, Paris, France
[6] Univ Paris Sud, Fac Med Paris Sud, INSERM, U 779, F-94275 Le Kremlin Bicetre, France
来源
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL | 2010年 / 95卷 / 05期
关键词
CDA II; SEC23B gene; COPII; genotype-phenotype relationship; CANDIDATE GENES; CDA-II; COAT; EXCLUSION; MEMBRANE; PROTEINS; DEFECT;
D O I
10.3324/haematol.2009.014985
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background The most frequent form of congenital dyserythropoietic anemia is the type II form. Recently it was shown that the vast majority of patients with congenital dyserythropoietic anemia type II carry mutations in the SEC23B gene. Here we established the molecular basis of 42 cases of congenital dyserythropoietic anemia type II and attempted to define a genotype-phenotype relationship. Design and Methods SEC23B gene sequencing analysis was performed to assess the diversity and incidence of each mutation in 42 patients with congenital dyserythropoietic anemia type II (25 described exclusively in this work), from the Italian and the French Registries, and the relationship of these mutations with the clinical presentation. To this purpose, we divided the patients into two groups: (i) patients with two missense mutations and (ii) patients with one nonsense and one missense mutation. Results We found 22 mutations of uneven frequency, including seven novel mutations. Compound heterozygosity for a missense and a nonsense mutation tended to produce a more severe clinical presentation, a lower reticulocyte count, a higher serum ferritin level, and, in some cases, more pronounced transfusion needs, than homozygosity or compound heterozygosity for two missense mutations. Homozygosity or compound heterozygosity for two nonsense mutations was never found. Conclusions This study allowed us to determine the most frequent mutations in patients with congenital dyserythropoietic anemia type II. Correlations between the mutations and various biological parameters suggested that the association of one missense mutation and one nonsense mutation was significantly more deleterious that the association of two missense mutations. However, there was an overlap between the two categories.
引用
收藏
页码:708 / 715
页数:8
相关论文
共 16 条
  • [1] The cisternae decorating the red blood cell membrane in congenital dyserythropoietic anemia (type II) originate from the endoplasmic reticulum
    Alloisio, N
    Texier, P
    Denoroy, L
    Berger, C
    delGiudice, EM
    Perrotta, S
    Iolascon, A
    Gilsanz, F
    Berger, G
    Guichard, J
    Masse, JM
    Debili, N
    BretonGorius, J
    Delaunay, J
    [J]. BLOOD, 1996, 87 (10) : 4433 - 4439
  • [2] CONGENITAL DYSERYTHROPOIETIC ANEMIA, TYPES 1 AND 2 - ABERRANT PATTERN OF ERYTHROCYTE-MEMBRANE PROTEINS IN CDA II, AS REVEALED BY 2-DIMENSIONAL POLYACRYLAMIDE-GEL ELECTROPHORESIS
    ANSELSTETTER, V
    HORSTMANN, HJ
    HEIMPEL, H
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 1977, 35 (02) : 209 - &
  • [3] Insights into COPII coat nucleation from the structure of Sec23•Sar1 complexed with the active fragment of sec31
    Bi, Xiping
    Mancias, Joseph D.
    Goldberg, Jonathan
    [J]. DEVELOPMENTAL CELL, 2007, 13 (05) : 635 - 645
  • [4] Structure of the Sec23/24-Sar1 pre-budding complex of the COPII vesicle coat
    Bi, XP
    Corpina, RA
    Goldberg, J
    [J]. NATURE, 2002, 419 (6904) : 271 - 277
  • [5] Congenital Dyserythropoietic Anemia Type II (CDAII) is Caused by Mutations in the SEC23B Gene
    Bianchi, Paola
    Fermo, Elisa
    Vercellati, Cristina
    Boschetti, Carla
    Barcellini, Wilma
    Iurlo, Alessandra
    Marcello, Anna Paola
    Righetti, Pier Giorgio
    Zanella, Alberto
    [J]. HUMAN MUTATION, 2009, 30 (09) : 1292 - 1298
  • [6] HEREDITARY ERYTHROBLASTIC MULTINUCLEARITY ASSOCIATED WITH A POSITIVE ACIDIFIED-SERUM TEST - A TYPE OF CONGENITAL DYSERYTHROPOIETIC ANAEMIA
    CROOKSTON, JH
    CROOKSTON, MC
    BURNIE, KL
    FRANCOMBE, WH
    DACIE, JV
    DAVIS, JA
    LEWIS, SM
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 1969, 17 (01) : 11 - +
  • [7] Congenital dyserythropoietic anemia type II (CDAII/HEMPAS): Where are we now?
    Denecke, Jonas
    Marquardt, Thorsten
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2009, 1792 (09): : 915 - 920
  • [8] INCOMPLETE SYNTHESIS OF N-GLYCANS IN CONGENITAL DYSERYTHROPOIETIC ANEMIA TYPE-II CAUSED BY A DEFECT IN THE GENE ENCODING ALPHA-MANNOSIDASE-II
    FUKUDA, MN
    MASRI, KA
    DELL, A
    LUZZATTO, L
    MOREMEN, KW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (19) : 7443 - 7447
  • [9] FUKUDA MN, 1987, J BIOL CHEM, V262, P7195
  • [10] Localization of the congenital dyserythropoietic anemia II locus to chromosome 20q11.2 by genomewide search
    Gasparini, P
    delGiudice, EM
    Delaunay, J
    Totaro, A
    Granatiero, M
    Melchionda, S
    Zelante, L
    Iolascon, A
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 61 (05) : 1112 - 1116