Submission Details

CENPE was first reported in relation to Microcephaly 13, primary, autosomal recessive in 2014 (Mirzaa et al., PMID: 24748105). This disease is characterized by microcephalic primordial dwarfism associated with developmental delay, simplified gyri and other isolated abnormalities. At least 2 missense variants have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in CENPE have been reported in individuals with the following disease entities: Microcephaly 13, primary, autosomal recessive (OMIM:616051). CENPE is also associated with Seckel syndrome (ORPHA:808) in orphanet. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism and inheritance pattern and phenotypic variability. Therefore, the following disease entities have been lumped into one disease entity: Microcephaly 13, primary, autosomal recessive (OMIM:616051). This gene-disease relationship is supported by a cenpe conditional knockout (KO) mouse model. KO mice fibroblast show mitotic chromosomal misalignment comparable to patient-derived LCLs (PMID: 12361599). In addition, embryonic tissue from CENP-meta KO fruit flies show disrupted mitosis and misaligned chromosomes (PMID: 10893249).Variants in this gene have been reported in at least 1 proband in 1 publication (PMID: 24748105). Variants in this gene segregated with disease in 1 additional family member. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship.
This classification was approved by the ClinGen brain malformations expert panel on 11/28/2023 (SOP Version 10 November 2023).