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

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• 作者：Annie Laquerriere^a ; ^b ; Marie Gonzales^c ; ^d ; Yoann Saillour^e ; ^f ; ^g ; Mara Cavallin^g ; ^h ; ⁱ ; Nicole Joyē^c ; ^d ; Chloé ; Quēlin^j ; Laurent Bidat^k ; Marc Dommergues^d ; ^l ; Ghislaine Plessis^m ; Ferechte Encha-Razavi^g ; ^h ; ⁿ ; Jamel Chelly^o ; ^p ; Nadia Bahi-Buisson^g ; ^h ; ⁱ ; ¹ ; ^{nadia.bahi-buisson@nck.aphp.fr" class="auth_mail" title="E-mail the corresponding author} ; Karine Poirier^e ; ^f ; ^g ; ¹
• 关键词：Microlissencephaly ; Microcephaly ; Migration disorder ; TUBB2B ; Fetal akinesia deformation sequence
• 刊名：European Journal of Medical Genetics
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：59
• 期：4
• 页码：249-256
• 全文大小：4272 K

文摘

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.

d="abspara0015">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.

d="abspara0020">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.

d="abspara0025">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.