E109K is a SEC23B founder mutation among Israeli Moroccan Jewish patients with congenital dyserythropoietic anemia type II.
OBJECTIVE
Congenital dyserythropoietic anemia (CDA) is characterized by ineffective erythropoiesis, binuclearity of erythroid precursors and secondary hemochromatosis. Recently, the gene mutated in CDA type II (CDA II), SEC23B, was identified. All Israeli patients with CDA II are of North African (mainly Moroccan) Jewish descent. We investigated the molecular basis of CDA II in those patients.


METHODS
Participants included 11 patients with CDA II from 8 apparently unrelated families. Clinical data were retrieved from medical files, and blood was collected for DNA analysis.


RESULTS
The majority of patients (10/11) were homozygous for a common SEC23B mutation (E109K). Haplotype analysis revealed a common genetic background in all patients. One patient was a compound heterozygote for the E109K mutation and a novel mutation, T710M. All patients were transfusion independent, with increasing iron overload with age. We estimate the E109K mutation to be 2,400 years old, in line with Jewish migration history.


CONCLUSIONS
Most CDA II patients in Israel are of Moroccan Jewish origin and carry a common SEC23B mutation, E109K, the first to be described as a founder mutation causing CDA II. As previously suggested, carrying 2 missense mutations is associated with a relatively nonsevere phenotype.
Department of Pediatrics B, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Achiya
A
Amir
Orly
O
Dgany
Tanya
T
Krasnov
Peretz
P
Resnitzky
Ronit
R
Mor-Cohen
Michael
M
Bennett
Alain
A
Berrebi
Hannah
H
Tamary
D000328:Adult; D000742:Anemia, Dyserythropoietic, Congenital / Q000208:ethnology / Q000235:genetics; D005260:Female; D018703:Founder Effect; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009018:Morocco / Q000208:ethnology; D020125:Mutation, Missense; D010375:Pedigree; D033921:Vesicular Transport Proteins / Q000235:genetics*
C543353:SEC23B protein, human; D033921:Vesicular Transport Proteins