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Autosomal recessive primary microcephaly due to ASPM mutations: An update
- Source :
- Human Mutation, Human Mutation, 2018, 39 (3), pp.319-332. ⟨10.1002/humu.23381⟩, Human mutation, Human Mutation, Wiley, 2018, 39 (3), pp.319-332. ⟨10.1002/humu.23381⟩, Human Mutation, Vol. 39, no. 3, p. 319-332 (2018), Human Mutation, Wiley, 2018, 39 (3), pp.319-332. 〈10.1002/humu.23381〉
- Publication Year :
- 2017
-
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 Here, we report 47 unpublished patients from 39 families carrying 28 new ASPM mutations, and conduct an exhaustive review of the molecular, clinical, neuroradiological and neuropsychological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. ispartof: Human Mutation vol:39 issue:3 pages:319-332 ispartof: location:United States status: published
- Subjects :
- 0301 basic medicine
Male
Microcephaly
MESH: Geography
Intellectual disability
ASPM
brain development
brain imaging
MESH: Cognition
[SDV.GEN] Life Sciences [q-bio]/Genetics
Spindle pole body
MESH: Magnetic Resonance Imaging
Cohort Studies
Neurodevelopmental disorder
Cognition
MESH: Nerve Tissue Proteins
MESH: Cohort Studies
Genetics (clinical)
MESH: Genetic Association Studies
Genetics
0303 health sciences
Geography
primary microcephaly
030305 genetics & heredity
Brain development
MESH: Infant
Magnetic Resonance Imaging
3. Good health
intellectual disability
Child, Preschool
Autosomal Recessive Primary Microcephaly
Brain size
Female
MESH: Mutation
Brain imaging
Nerve Tissue Proteins
[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics
Biology
MESH: Microcephaly
Primary microcephaly
03 medical and health sciences
medicine
Humans
Family
Gene
MESH: Family
Genetic Association Studies
030304 developmental biology
Centrosome
MCPH
[SDV.GEN]Life Sciences [q-bio]/Genetics
MESH: Humans
Genetic heterogeneity
MESH: Child, Preschool
Infant
medicine.disease
MESH: Male
030104 developmental biology
centrosome
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Mutation
Human medicine
[ SDV.GEN ] Life Sciences [q-bio]/Genetics
MESH: Female
Subjects
Details
- ISSN :
- 10981004 and 10597794
- Volume :
- 39
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Human mutation
- Accession number :
- edsair.doi.dedup.....180ab4deec46299105e355e99a59a088