Clinical Report
Recurrent RTTN mutation leading to severe microcephaly, polymicrogyria and growth restriction

https://doi.org/10.1016/j.ejmg.2018.08.001Get rights and content

Abstract

Autosomal recessive missense Rotatin (RTTN) mutations are responsible for syndromic forms of malformation of cortical development, ranging from isolated polymicrogyria to microcephaly associated with primordial dwarfism and other major malformations.

We identified, by trio based whole exome sequencing, a homozygous missense mutation in the RTTN gene (c.2953A > G; p.(Arg985Gly)) in one Moroccan patient from a consanguineous family. The patient showed early onset primary microcephaly, detected in the fetal period, postnatal growth restriction, encephalopathy with hyperkinetic movement disorders and self-injurious behavior with sleep disturbance. Brain MRI showed an extensive dysgyria associated with nodular heterotopia, large interhemispheric arachnoid cyst and corpus callosum hypoplasia.

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Conclusion

Our data suggest that the p.(Arg985Gly) RTTN mutation may be recurrent and lead to a severe phenotype, characterized by complex brain phenotype with microcephaly dwarfism. Although the mutation does not affect the Armadillo domain, we anticipate that such a variation located in the “medium-domain” of RTTN may have severe consequences on Rotatin function during development.

Funding sources

Research reported in this publication was supported by the Agence Nationale de la Recherche [ANR-16-CE16-0011 MC, AB, NBB]; the Fondation Maladies Rares; and DESIRE [grant agreement 602531]; and COST Action Proposal OC-2016-1-20862 “European Network on Brain Malformations”.

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