It has long been recognized that Down syndrome (DS) is associated with macrocytosis.
Red blood cells (RBCs) from humans with DS are on average about 8-10 fL larger than controls. In one study of young adults with DS, about 18% met criteria for macrocytosis (MCV > 100 fL) (see graphic).
Macrocytosis has also been reported in mouse models of DS, including the Ts65D mouse, the TC1 mouse and the Ts1Cje mouse, suggesting a gene dosage effect.
In bone marrow transplantation studies, bone marrow from the Ts65Dn mouse resulted in macrocytosis in wild type recipient mice, indicating that the defect occurs by a cell-autonomous mechanism.
There are a total of about 222 protein-coding genes in trisomy of human chromosome 21 (Hsa21). The 3 mouse models of DS help to narrow down the responsible region for macrocytosis (blue shade in graphic).
References:
| Citation | PubMed Link | |
|---|---|---|
| Macrocytosis in Down’s syndrome. Lancet. 1969;1:89 | Link | Link |
| Leukopenia, macrocytosis, and thrombocytopenia occur in young adults with Down syndrome. Gene. 2022:835:146663 | Link | Link |
| Highly penetrant myeloproliferative disease in the Ts65Dn mouse model of Down syndrome. Blood. 2008;111:767-75 | Link | Link |
| Perturbed hematopoiesis in the Tc1 mouse model of Down syndrome. Blood. 2010;115(14):2928-37. | Link | Link |
| Hematopoietic defects in the Ts1Cje mouse model of Down syndrome. Blood. 2009;113:1929-37 | Link | Link |