[P1-189] Two Siblings With “TUBB3 E410K Syndrome”.
[Background] Congenital cranial dysinnervation disorders (CCDDs) are a heterogeneous group of congenital, non-progressive neuromuscular disorders characterized by eye, eyelid or facial movement. Mutations in different genes have been identified as the cause of CCDD.
[Purpose] To identify the causative mutation in two siblings with CCDD.
[Methods] Two affected siblings and their asymptomatic parents underwent whole exome sequencing.
[Results]Clinical phenotype ranged within the affected siblings. Both patients presented abnormal eye, eyelid and facial weakness, but these symptoms were relatively mild in the younger brother. On the other hand, the younger brother additionally presented vocal cord paralysis, failure to thrive, and hypotonia. A heterozygous missense mutation c.1228G>A which result in TUBB3 E410K amino acid substitution was identified in affected siblings, but it was absent in both parents. β-Ⅲ-tubulin (TUBB3) is a neuron-specific isotype of the microtubule protein, required for axonal guidance and maintenance in the central and peripheral nervous system. It was reported that a heterozygous c.1228G>A mutation (E410K) in the TUBB3 causes the “TUBB3 E410K syndrome” characterized by congenital, non-progressive ophthalmoplegia, facial weakness, intellectual and social disabilities, and Kallmann syndrome.
[Conclusions] The recurrence of the same mutation in the two siblings suggests the existence of germline mosaicism in one of the asymptomatic parents. This information is useful for genetic counseling with this syndrome.
[Purpose] To identify the causative mutation in two siblings with CCDD.
[Methods] Two affected siblings and their asymptomatic parents underwent whole exome sequencing.
[Results]Clinical phenotype ranged within the affected siblings. Both patients presented abnormal eye, eyelid and facial weakness, but these symptoms were relatively mild in the younger brother. On the other hand, the younger brother additionally presented vocal cord paralysis, failure to thrive, and hypotonia. A heterozygous missense mutation c.1228G>A which result in TUBB3 E410K amino acid substitution was identified in affected siblings, but it was absent in both parents. β-Ⅲ-tubulin (TUBB3) is a neuron-specific isotype of the microtubule protein, required for axonal guidance and maintenance in the central and peripheral nervous system. It was reported that a heterozygous c.1228G>A mutation (E410K) in the TUBB3 causes the “TUBB3 E410K syndrome” characterized by congenital, non-progressive ophthalmoplegia, facial weakness, intellectual and social disabilities, and Kallmann syndrome.
[Conclusions] The recurrence of the same mutation in the two siblings suggests the existence of germline mosaicism in one of the asymptomatic parents. This information is useful for genetic counseling with this syndrome.