ArticleHuman mutation2020
Digenic inheritance of human primary microcephaly delineates centrosomal and non-centrosomal pathways.
Article in Human mutation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Non-syndromic premature ovarian insufficiency associated with monoallelic LIG4 mutation via haploinsufficiency.Journal of ovarian research · 2026Article
- Article
- Clinical genomics expands the link between erroneous cell division, primary microcephaly and intellectual disability.Neurogenetics · 2024Article
- Investigating the effects of a single ASPM variant (c.8508_8509) on brain architecture among siblings in a consanguineous Pakistani family.Molecular biology reports · 2024Article
- Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size.Cells · 2023Review
- Congenital hydrocephalus: new Mendelian mutations and evidence for oligogenic inheritance.Human genomics · 2023Article
- Expanding the Phenotype ofJournal of clinical research in pediatric endocrinology · 2023Article
- Review
- The neurological and non-neurological roles of the primary microcephaly-associated protein ASPM.Frontiers in neuroscience · 2023Review
- Teleost Fish and Organoids: Alternative Windows Into the Development of Healthy and Diseased Brains.Frontiers in molecular neuroscience · 2022Review
- Identifying digenic disease genes via machine learning in the Undiagnosed Diseases Network.American journal of human genetics · 2021Article
- Phenotypes and genotypes in non-consanguineous and consanguineous primary microcephaly: High incidence of epilepsy.Molecular genetics & genomic medicine · 2021Article
- Modifier Genes in Microcephaly: A Report onGenes · 2021Article
- Molecular Genetics of Microcephaly Primary Hereditary: An Overview.Brain sciences · 2021Review
- Article
- Digenic inheritance of human primary microcephaly delineates centrosomal and non-centrosomal pathways.Human mutation · 2020Article
- Dissecting the Genetic and Etiological Causes of Primary Microcephaly.Frontiers in neurology · 2020Review
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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 was carried by six centrosomal genes. Allelic frequencies were consistent with digenic inheritance. In zebrafish, non-centrosomal gene casc5 -/- produced a severe PM phenotype, that was not modified by centrosomal genes aspm or wdr62 invalidation. A digenic, quadriallelic PM phenotype was produced by aspm and wdr62. Our observations provide strong evidence for digenic inheritance of human PM, involving centrosomal genes. Absence of genetic interaction between casc5 and aspm or wdr62 further delineates centrosomal and non-centrosomal pathways in PM.
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