CEP152 was first reported in relation to autosomal recessive Microcephaly with or without short stature in 2010 (Guernsey et al., PMID: 20598275). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no differences in molecular mechanism and inheritance pattern. Therefore, the following disease entities have been lumped into one, Microcephaly 9, primary (OMIM: 614852), and Seckel syndrome 5 (OMIM: 613823). Microcephaly with or without short stature is a disorder of fetal brain growth. Individuals have reduced head circumference at birth and variable degrees of intellectual impairment. Clinical features can also include a typical 'bird-head' facial appearance of Seckel syndrome and may include short stature. 7 variants (missense, nonsense, frameshift, splice site) that have been reported in 11 probands in 2 publications (PMIDs: 21131937, 20598275) and are included in this curation. Of note, one reported case was identified to carry two cis homozygous variants in the CEP152 gene. This proband was is included in the curation but not scored. The mechanism of pathogenicity appears to be LOF. This gene-disease association is also supported by expression studies and a functional alteration study (PMIDs: 21131937, 20598275, 35259752). Cep152 was found to be expressed in developing mice brains and additionally has altered morphology and mitotic function. In summary, CEP152 is definitively associated with autosomal recessive Microcephaly with or without short stature. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Brain Malformations Gene Curation Expert Panel on the meeting date 06/28/22 (SOP Version 8).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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