Dissecting the Genetic and Etiological Causes of Primary Microcephaly.
cell cycle
genetics
microcephaly
neurogenesis
rare disease (RD)
Journal
Frontiers in neurology
ISSN: 1664-2295
Titre abrégé: Front Neurol
Pays: Switzerland
ID NLM: 101546899
Informations de publication
Date de publication:
2020
2020
Historique:
received:
09
06
2020
accepted:
09
09
2020
entrez:
12
11
2020
pubmed:
13
11
2020
medline:
13
11
2020
Statut:
epublish
Résumé
Autosomal recessive primary microcephaly (MCPH; "small head syndrome") is a rare, heterogeneous disease arising from the decreased production of neurons during brain development. As of August 2020, the Online Mendelian Inheritance in Man (OMIM) database lists 25 genes (involved in molecular processes such as centriole biogenesis, microtubule dynamics, spindle positioning, DNA repair, transcriptional regulation, Wnt signaling, and cell cycle checkpoints) that are implicated in causing MCPH. Many of these 25 genes were only discovered in the last 10 years following advances in exome and genome sequencing that have improved our ability to identify disease-causing variants. Despite these advances, many patients still lack a genetic diagnosis. This demonstrates a need to understand in greater detail the molecular mechanisms and genetics underlying MCPH. Here, we briefly review the molecular functions of each MCPH gene and how their loss disrupts the neurogenesis program, ultimately demonstrating that microcephaly arises from cell cycle dysregulation. We also explore the current issues in the genetic basis and clinical presentation of MCPH as additional avenues of improving gene/variant prioritization. Ultimately, we illustrate that the detailed exploration of the etiology and inheritance of MCPH improves the predictive power in identifying previously unknown MCPH candidates and diagnosing microcephalic patients.
Identifiants
pubmed: 33178111
doi: 10.3389/fneur.2020.570830
pmc: PMC7593518
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
570830Informations de copyright
Copyright © 2020 Jean, Stuart and Tarailo-Graovac.
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