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Autosomal recessive primary microcephaly due to ASPM mutations: An update
Author(s) -
Létard Pascaline,
Drunat Séverine,
Vial Yoann,
Duerinckx Sarah,
Ernault Anais,
Amram Daniel,
Arpin Stéphanie,
Bertoli Marta,
Busa Tiffany,
Ceulemans Berten,
Desir Julie,
DocoFenzy Martine,
Elalaoui Siham Chafai,
Devriendt Koenraad,
Faivre Laurence,
Francannet Christine,
Geneviève David,
Gérard Marion,
Gitiaux Cyril,
Julia Sophie,
Lebon Sébastien,
Lubala Toni,
MathieuDramard Michèle,
Maurey Hélène,
Metreau Julia,
Nasserereddine Sanaa,
Nizon Mathilde,
Pierquin Geneviève,
Pouvreau Nathalie,
RivierRingenbach Clothilde,
Rossi Massimiliano,
Schaefer Elise,
Sefiani Abdelaziz,
Sigaudy Sabine,
Sznajer Yves,
Tunca Yusuf,
Guilmin Crepon Sophie,
Alberti Corinne,
ElmalehBergès Monique,
Benzacken Brigitte,
Wollnick Bernd,
Woods C. Geoffrey,
Rauch Anita,
Abramowicz Marc,
El Ghouzzi Vincent,
Gressens Pierre,
Verloes Alain,
Passemard Sandrine
Publication year - 2018
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23381
Subject(s) - microcephaly , biology , intellectual disability , genetics
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 Here, we report 47 unpublished patients from 39 families carrying 28 new ASPM mutations, and conduct an exhaustive review of the molecular, clinical, neuroradiological, and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.