Autosomal recessive primary microcephaly due to ASPM mutations: An update
Copyright policy )Autosomal recessive primary microcephaly due to ASPM mutations: An update
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 Here, we report 47 unpublished patients from 39 families carrying 28 new ASPM mutations, and conduct an exhaustive review of the molecular, clinical, neuroradiological, and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.
- Assistance Publique -Hopitaux De Paris France
- University of Cambridge United Kingdom
- University of Montpellier France
- Université Libre de Bruxelles Belgium
- French National Centre for Scientific Research France
Male, MESH: Geography, Intellectual disability, PROTEIN-TRUNCATING MUTATIONS, ASPM, MESH: Cognition, Genetics & genetic processes, brain development, brain imaging, [SDV.GEN] Life Sciences [q-bio]/Genetics, Nerve Tissue Proteins -- genetics, MESH: Magnetic Resonance Imaging, Cohort Studies, Génétique & processus génétiques, Cognition, Microcephaly -- epidemiology -- genetics, MESH: Child, MAPS, Mutation -- genetics, MESH: Nerve Tissue Proteins, PAKISTANI FAMILIES, Child, MESH: Cohort Studies, MESH: Genetic Association Studies, Genetics & Heredity, Geography, primary microcephaly, Sciences bio-médicales et agricoles, MESH: Infant, Brain development, Life sciences, Magnetic Resonance Imaging, intellectual disability, Child, Preschool, Sciences du vivant, Microcephaly, Female, Life Sciences & Biomedicine, 570, MESH: Mutation, 610, Brain imaging, Nerve Tissue Proteins, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, DIAGNOSIS, PATIENT, MESH: Microcephaly, 3105 Genetics, Primary microcephaly, Humans, Family, Preschool, MESH: Family, Genetic Association Studies, Centrosome, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0604 Genetics, MCPH, MESH: Humans, Science & Technology, 3202 Clinical sciences, Infant, 1103 Clinical Sciences, GENE, MESH: Male, EVOLUTION, centrosome, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, BRAIN SIZE, MESH: Female
Male, MESH: Geography, Intellectual disability, PROTEIN-TRUNCATING MUTATIONS, ASPM, MESH: Cognition, Genetics & genetic processes, brain development, brain imaging, [SDV.GEN] Life Sciences [q-bio]/Genetics, Nerve Tissue Proteins -- genetics, MESH: Magnetic Resonance Imaging, Cohort Studies, Génétique & processus génétiques, Cognition, Microcephaly -- epidemiology -- genetics, MESH: Child, MAPS, Mutation -- genetics, MESH: Nerve Tissue Proteins, PAKISTANI FAMILIES, Child, MESH: Cohort Studies, MESH: Genetic Association Studies, Genetics & Heredity, Geography, primary microcephaly, Sciences bio-médicales et agricoles, MESH: Infant, Brain development, Life sciences, Magnetic Resonance Imaging, intellectual disability, Child, Preschool, Sciences du vivant, Microcephaly, Female, Life Sciences & Biomedicine, 570, MESH: Mutation, 610, Brain imaging, Nerve Tissue Proteins, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, DIAGNOSIS, PATIENT, MESH: Microcephaly, 3105 Genetics, Primary microcephaly, Humans, Family, Preschool, MESH: Family, Genetic Association Studies, Centrosome, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0604 Genetics, MCPH, MESH: Humans, Science & Technology, 3202 Clinical sciences, Infant, 1103 Clinical Sciences, GENE, MESH: Male, EVOLUTION, centrosome, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, BRAIN SIZE, MESH: Female
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