Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephalyReportar como inadecuado

Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

* Corresponding author 1 Département de pathologie et biologie cellulaire 2 Endothélium microvasculaire et lésions cérébrales néonatales 3 Laboratoire de Pathologie 4 Institut Cochin 5 IHU - Imagine - Institut des maladies génétiques 6 Service de Biologie du Développement 7 Department of Genetics 8 Service d-Anatomie et de Cytologie Pathologiques 9 Children’s Neurosciences Department 10 Laboratoire de biochimie et génétique moléculaire 11 Center for Human Genetics 12 Département Génétique Médicale-Maternité 13 Service d-Anatomie Pathologique Générale 14 Service de Génétique et d-Embryologie Médicales 15 Laboratoire de Pathologie Foetale 16 Services d-Anatomopathologie et de Génétique 17 Service d-Anatomie Pathologique 18 Service d-anatomie et cytologie pathologiques Rennes

Abstract : Complex cortical malformations associated with mutations in tubulin genes are commonly referred to as -Tubulinopathies-. To further characterize the mutation frequency and phenotypes associated with tubulin mutations, we studied a cohort of 60 foetal cases. Twenty-six tubulin mutations were identified, of which TUBA1A mutations were the most prevalent 19 cases, followed by TUBB2B 6 cases and TUBB3 one case. Three subtypes clearly emerged. The most frequent n = 13 was microlissencephaly with corpus callosum agenesis, severely hypoplastic brainstem and cerebellum. The cortical plate was either absent 6-13, with a 2–3 layered pattern 5-13 or less frequently thickened 2-13, often associated with neuroglial overmigration 4-13. All cases had voluminous germinal zones and ganglionic eminences. The second subtype was lissencephaly n = 7, either classical 4-7 or associated with cerebellar hypoplasia 3-7 with corpus callosum agenesis 6-7. All foetuses with lissencephaly and cerebellar hypoplasia carried distinct TUBA1A mutations, while those with classical lissencephaly harbored recurrent mutations in TUBA1A 3 cases or TUBB2B 1 case. The third group was polymicrogyria-like cortical dysplasia n = 6, consisting of asymmetric multifocal or generalized polymicrogyria with inconstant corpus callosum agenesis 4-6 and hypoplastic brainstem and cerebellum 3-6. Polymicrogyria was either unlayered or 4-layered with neuronal heterotopias 5-6 and occasional focal neuroglial overmigration 2-6. Three had TUBA1A mutations and 3 TUBB2B mutations. Foetal TUBA1A tubulinopathies most often consist in microlissencephaly or classical lissencephaly with corpus callosum agenesis, but polymicrogyria may also occur. Conversely, TUBB2B mutations are responsible for either polymicrogyria 4-6 or microlissencephaly 2-6.

Keywords : Polymicrogyria Microcephaly Tubulin genes Microlissencephaly Lissencephaly

Autor: Catherine Fallet-Bianco - Annie Laquerrière - Karine Poirier - Ferechte Razavi - Fabien Guimiot - Patricia Dias - Laurence Loeui



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