Codanin 1 (CDAN1; MIM# 224120), also known as Discs Lost Homolog or DLT, is a negative regulator of chromatin replication and plays an important role in erythropoiesis. CDAN1 is a gene associated with autosomal recessive congenital dyserythropoietic anemia type 1a (CDA1, AR; MIM# 224120). The molecular etiology of CDA1 was first described by Dgany, et al in 2002 [PMID:12434312] and has been described in many affected individuals since [PMID:29599085, 29668551, 34782754, 29031773, 24196372, 31900952, 35012925, 16098079, 33401150, 30786798]. Variants are nonsense, frameshift, and missense. Loss-of-function is the proposed mechanism of disease, however no homozygous or compound het null variants have been identified in humans and complete knockout is early embryonic lethal in mice [PMID:34234691], suggesting that some residual function is required. Additionally, many missense variants identified in affected individuals have not been functionally evaluated for presumed partial loss-of-function. Distinctive erythroblast abnormalities are considered pathognomonic for CDA1, including spongy heterochromatin, internuclear chromatin bridges, and invaginated nuclear pores [PMID:30836435]. CDA1 is often diagnosed in childhood, but a fetal sub-type presents with hemolytic anemia and additional variable features including hydrops fetalis, small for gestational age, hepatosplenomegaly, pulmonary hypertension, neonatal jaundice, and occasional distal limb abnormalities such as toe syndactyly and nail hypoplasia [PMID: 20301759]. Genetic evidence for congenital dyserythropoietic anemia type 1a was scored at the maximum of 12 points. Functional evidence including mouse and zebrafish models recapitulating the observed human phenotype and biochemical function [PMID: 34234691] were scored for an additional 2.5 points. Given this and its replication in the literature over time, the association with the CDAN1 gene and congenital dyserythropoietic anemia type 1a is curated as Definitive by the Prenatal Gene Curation Expert Panel.
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