De novo TUBB2B mutation causes fetal akinesia deformation sequence with microlissencephaly: an unusual presentation of tubulinopathy - Archive ouverte HAL Access content directly
Journal Articles European Journal of Medical Genetics Year : 2015

De novo TUBB2B mutation causes fetal akinesia deformation sequence with microlissencephaly: an unusual presentation of tubulinopathy

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Abstract

Tubulinopathies are increasingly emerging major causes underlying complex cerebral malformations, particularly in case of microlissencephaly often associated with hypoplastic or absent corticospinal tracts. Fetal akinesia deformation sequence (FADS) refers to a clinically and genetically heterogeneous group of disorders with congenital malformations related to impaired fetal movement. We report on an early foetal case with FADS and microlissencephaly due to TUBB2B mutation. Neuropathological examination disclosed virtually absent cortical lamination, foci of neuronal overmigration into the leptomeningeal spaces, corpus callosum agenesis, cerebellar and brainstem hypoplasia and extremely severe hypoplasia of the spinal cord with no anterior and posterior horns and almost no motoneurons. At the cellular level, the p.Cys239Phe TUBB2B mutant leads to tubulin heterodimerization impairment, decreased ability to incorporate into the cytoskeleton, microtubule dynamics alteration, with an accelerated rate of depolymerization. To our knowledge, this is the first case of microlissencephaly to be reported presenting with a so severe and early form of FADS, highlighting the importance of tubulin mutation screening in the context of FADS with microlissencephaly.
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Format : Figure, Image
Origin : Files produced by the author(s)

Dates and versions

hal-01259440 , version 1 (06-06-2016)

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Annie Laquerrière, Marie Gonzales, Yoann Saillour, Mara Cavallin, Nicole Joyē, et al.. De novo TUBB2B mutation causes fetal akinesia deformation sequence with microlissencephaly: an unusual presentation of tubulinopathy. European Journal of Medical Genetics, 2015, 59 (4), pp.249-256. ⟨10.1016/j.ejmg.2015.12.007⟩. ⟨hal-01259440⟩
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