Objective: Here we want to present one family in which there is diverse phenotype with probable pathogenic novel mutation in TUBB4A gene.

Background: Mutation in gene TUBB4A leads to diverse clinical phenotype, from DYT4 or whispering dysphonia and generalized dystonia with normal magnetic resonance imaging (MRI) of the endocranium, spastic paraplegia with isolated hypomyelination on MRI of the endocranium to early onset of intellectual and motor dissability with epilepsy and severe encephalopathy.

Method: All patients were neurological examined and MRI of the endocranium were done for all female patients. Genetic mutation in TUBB4A gene was identified with next generation sequencing and confirmation of detected TUBB4A variant was done by Sanger sequencing after PCR amplification of target region.

Results: Two sisters had phenotype of spastic quadriparesis with results of MRI of the endocranium indicating that there is bilateral hyperintensities on T2W/FLAIR along the corticospinal tract. One of them had also spastic dysarthria and dystonia of the jaw. The daughter of one of them had spastic paraparesis. Brother of the two sisters had generalized dystonia with flexion of the trunk and dystonia of the legs. Clinical exome sequencing of these patients indicated in exon 4 of TUBB4A gene the presence of novel missense likely pathogenic heterozygous variant p.Phe341Leu (c.1021T>C, NM_006087.4). Other members of the family who were healthy were negative for this mutation.

Conclusion: In this study, we identified a novel likely pathogenic TUB44A mutation by clinical exome sequencing and presented that the spectrum of phenotype could be diverse across a single family.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/mutation-in-tubb4a-causing-from-dystonia-to-spastic-quadriparesis-across-one-family/