Abstract:

Tubulinopathy is a rare autosomal recessive hereditary disease caused by TBCD variation and characterized by early-onset progressive encephalopathy. The patient was a boy aged 11 months. At the age of 8 months, he had a febrile convulsion which was a focal seizure. It appeared after bathing or fever in his early stage, and convulsions occurred at any time in the later stage. Since the onset of the disease, the psychomotor function has been progressively retrogressed. At the age of 11 months, the activity of his limbs gradually decreased, and the results of electromyography showed extensive neurogenic damage. The cranial magnetic resonance imaging showed the widened sulcus, thinned corpus callosum and cerebral dysplasia. The results of whole exome gene sequencing indicated that the child carried complex heterozygous variations of TBCD gene: a heterozygous missense variation of c.230A>G (p.H77R) in exon 2 and a heterozygous termination variation of c.1306C>T (p.R436*, 757) in exon 13. The two variants have not been reported. The father carried c.230A>G variation, and the mother carried c.1306C>T variation. Finally, the child was diagnosed with tubulinopathy with atypical spinal muscular atrophy (SMA). At the age of 1 year and 4 months, the child was treated with four antiepileptic drugs and had fewer convulsions. The phenotype in this case was accompanied by atypical SMA, which enriched the clinical phenotypes spectrum of the disease. A new termination mutation and a new missense mutation detected by genetic testing enlarged the TBCD gene variation spectrum.

Key words: TBCD gene, tubulinopathy, early-onset progressive encephalopathy, spinal muscular atrophy, child