Title |
Autosomal recessive primary microcephaly due to ASPM mutations: An update
|
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Published in |
Human Mutation, January 2018
|
DOI | 10.1002/humu.23381 |
Pubmed ID | |
Authors |
Pascaline Létard, Séverine Drunat, Yoann Vial, Sarah Duerinckx, Anais Ernault, Daniel Amram, Stéphanie Arpin, Marta Bertoli, Tiffany Busa, Berten Ceulemans, Julie Desir, Martine Doco‐Fenzy, Siham Chafai Elalaoui, Koenraad Devriendt, Laurence Faivre, Christine Francannet, David Geneviève, Marion Gérard, Cyril Gitiaux, Sophie Julia, Sébastien Lebon, Toni Lubala, Michèle Mathieu‐Dramard, Hélène Maurey, Julia Metreau, Sanaa Nasserereddine, Mathilde Nizon, Geneviève Pierquin, Nathalie Pouvreau, Clothilde Rivier‐Ringenbach, Massimiliano Rossi, Elise Schaefer, Abdelaziz Sefiani, Sabine Sigaudy, Yves Sznajer, Yusuf Tunca, Sophie Guilmin Crepon, Corinne Alberti, Monique Elmaleh‐Bergès, Brigitte Benzacken, Bernd Wollnick, C. Geoffrey Woods, Anita Rauch, Marc Abramowicz, Vincent El Ghouzzi, Pierre Gressens, Alain Verloes, Sandrine Passemard |
Abstract |
Autosomal recessive microcephaly or MicroCephaly Primary Hereditary (MCPH) is a genetically heterogeneous neurodevelopmental disorder characterized by a reduction in brain volume, indirectly measured by an occipitofrontal circumference (OFC) 2 standard deviations or more below the age- and sex-matched mean (-2SD) at birth and -3SD after 6 months, and leading to intellectual disability of variable severity. The Abnormal SPindle-like Microcephaly gene (ASPM), the human ortholog of the Drosophila melanogaster 'abnormal spindle' gene (asp), encodes ASPM, a protein localized at the centrosome of apical neuroprogenitor cells and involved in spindle pole positioning during neurogenesis. Loss-of-function mutations in ASPM cause MCPH5, which affects the majority of all MCPH patients worldwide. Here, we report 47 unpublished patients from 39 families carrying 28 new ASPM mutations, and conduct an exhaustive review of the molecular, clinical, neuroradiological and neuropsychological features of the 282 families previously reported (with 161 distinct ASPM mutations). Furthermore, we show that ASPM-related microcephaly is not systematically associated with intellectual deficiency and discuss the association between the structural brain defects (strong reduction in cortical volume and surface area) that modify the cortical map of these patients and their cognitive abilities. This article is protected by copyright. All rights reserved. |
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Country | Count | As % |
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United States | 1 | 33% |
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Scientists | 1 | 33% |
Mendeley readers
Geographical breakdown
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Student > Master | 13 | 14% |
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Researcher | 8 | 9% |
Professor | 6 | 6% |
Other | 14 | 15% |
Unknown | 27 | 29% |
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Neuroscience | 8 | 9% |
Psychology | 3 | 3% |
Other | 11 | 12% |
Unknown | 33 | 35% |