Digenic inheritance of human primary microcephaly delineates centrosomal and non-centrosomal pathways.

ABSTRACT: Primary microcephaly (PM) is characterized by a small head since birth and is vastly heterogeneous both genetically and phenotypically. While most cases are monogenic, genetic interactions between Aspm and Wdr62 have recently been described in a mouse model of PM. Here, we used two complementary, holistic in vivo approaches: high throughput DNA sequencing of multiple PM genes in human patients with PM, and genome-edited zebrafish modeling for the digenic inheritance of PM. Exomes of patients with PM showed a significant burden of variants in 75 PM genes, that persisted after removing monogenic causes of PM (e.g., biallelic pathogenic variants in CEP152). This observation was replicated in an independent cohort of patients with PM, where a PM gene panel showed in addition that the burden wa

SUBMITTER: Duerinckx S 

PROVIDER: S-EPMC7496698 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature