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P.11 The phenotype in E410K Beta-tubulin isotype 3 mutations
  1. M Sabah,
  2. E Young,
  3. A Fryer,
  4. S Ellard,
  5. N J Gutowski
  1. The Royal Devon and Exeter Hospital, Exeter, UK

Abstract

Introduction The Congenital Cranial Dysinnervation Disorders are congenital, non-progressive disorders that result from developmental abnormalities of one or more cranial nerves/nuclei with primary or secondary dysinnervation and include Duane's syndrome, Möbius syndrome, Congenital Fibrosis of the External Ocular Muscles (CFEOM) and Congenital ptosis. Cases are obtained for phenotype/genotype research via a number of reporting mechanisms including the British Neurological Surveillance Unit. Recently mutations in the β-tubulin isotype 3 (TUBB3) gene have been reported to produce several phenotypes depending on the particular mutation.

Methods Sequence analysis of the TUBB3 gene was undertaken in Congenital Cranial Dysinnervation Disorder families with CFEOM phenotypes for which a genetic cause had not previously been determined.

Results Four affected individuals in two families were identified to have a previously reported heterozygous missense TUBB3 mutation, E410K. The phenotype in all individuals consisted of CFEOM with some variability but preserved eye abduction bilaterally and striking facial weakness. Other findings included developmental delay, corpus callosum hypoplasia and an adult with sensory axonal neuropathy.

Conclusion There are dramatic genotype/phenotype correlations depending on the particular TUBB3 mutation. Although there was striking facial weakness in our cases with ocular involvement they did not fulfil the criteria for Möbius syndrome as abduction was preserved.

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