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Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size

Primary microcephalies (PMs) are defects in brain growth that are detectable at or before birth and are responsible for neurodevelopmental disorders. Most are caused by biallelic or, more rarely, dominant mutations in one of the likely hundreds of genes encoding PM proteins, i.e., ubiquitous centros...

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Autores principales: Farcy, Sarah, Hachour, Hassina, Bahi-Buisson, Nadia, Passemard, Sandrine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10340463/
https://www.ncbi.nlm.nih.gov/pubmed/37443841
http://dx.doi.org/10.3390/cells12131807
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author Farcy, Sarah
Hachour, Hassina
Bahi-Buisson, Nadia
Passemard, Sandrine
author_facet Farcy, Sarah
Hachour, Hassina
Bahi-Buisson, Nadia
Passemard, Sandrine
author_sort Farcy, Sarah
collection PubMed
description Primary microcephalies (PMs) are defects in brain growth that are detectable at or before birth and are responsible for neurodevelopmental disorders. Most are caused by biallelic or, more rarely, dominant mutations in one of the likely hundreds of genes encoding PM proteins, i.e., ubiquitous centrosome or microtubule-associated proteins required for the division of neural progenitor cells in the embryonic brain. Here, we provide an overview of the different types of PMs, i.e., isolated PMs with or without malformations of cortical development and PMs associated with short stature (microcephalic dwarfism) or sensorineural disorders. We present an overview of the genetic, developmental, neurological, and cognitive aspects characterizing the most representative PMs. The analysis of phenotypic similarities and differences among patients has led scientists to elucidate the roles of these PM proteins in humans. Phenotypic similarities indicate possible redundant functions of a few of these proteins, such as ASPM and WDR62, which play roles only in determining brain size and structure. However, the protein pericentrin (PCNT) is equally required for determining brain and body size. Other PM proteins perform both functions, albeit to different degrees. Finally, by comparing phenotypes, we considered the interrelationships among these proteins.
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spelling pubmed-103404632023-07-14 Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size Farcy, Sarah Hachour, Hassina Bahi-Buisson, Nadia Passemard, Sandrine Cells Review Primary microcephalies (PMs) are defects in brain growth that are detectable at or before birth and are responsible for neurodevelopmental disorders. Most are caused by biallelic or, more rarely, dominant mutations in one of the likely hundreds of genes encoding PM proteins, i.e., ubiquitous centrosome or microtubule-associated proteins required for the division of neural progenitor cells in the embryonic brain. Here, we provide an overview of the different types of PMs, i.e., isolated PMs with or without malformations of cortical development and PMs associated with short stature (microcephalic dwarfism) or sensorineural disorders. We present an overview of the genetic, developmental, neurological, and cognitive aspects characterizing the most representative PMs. The analysis of phenotypic similarities and differences among patients has led scientists to elucidate the roles of these PM proteins in humans. Phenotypic similarities indicate possible redundant functions of a few of these proteins, such as ASPM and WDR62, which play roles only in determining brain size and structure. However, the protein pericentrin (PCNT) is equally required for determining brain and body size. Other PM proteins perform both functions, albeit to different degrees. Finally, by comparing phenotypes, we considered the interrelationships among these proteins. MDPI 2023-07-07 /pmc/articles/PMC10340463/ /pubmed/37443841 http://dx.doi.org/10.3390/cells12131807 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Farcy, Sarah
Hachour, Hassina
Bahi-Buisson, Nadia
Passemard, Sandrine
Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size
title Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size
title_full Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size
title_fullStr Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size
title_full_unstemmed Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size
title_short Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size
title_sort genetic primary microcephalies: when centrosome dysfunction dictates brain and body size
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10340463/
https://www.ncbi.nlm.nih.gov/pubmed/37443841
http://dx.doi.org/10.3390/cells12131807
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