LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

Dissecting the Genetic and Etiological Causes of Primary Microcephaly

Photo by camstejim from unsplash

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… Click to show full abstract

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.

Keywords: primary microcephaly; mcph; causes primary; genetic etiological; dissecting genetic; etiological causes

Journal Title: Frontiers in Neurology
Year Published: 2020

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.