Background Recessive TBC1D24 gene mutations have been described in two families: an Italian family afflicted with familial infantile myoclonic epilepsy, and an Arab family with focal epilepsy and intellectual disability syndrome. The patients in the Italian family were compound heterozygous for two mutations, whereas those in the Arab family were homozygotes. All three mutations were missense and were determined to be loss of function. We conducted a gene search in a family we previously reported with a severe, lethal epileptic encephalopathy mapping at 16pter-p13.3.

Methods Exome sequencing and subsequent Sanger sequencing of TBC1D24 exons were conducted. Sanger sequencing was used to determine the structures of novel mRNA isoforms. The abundance of mRNA isoforms was assessed via real-time quantitative PCR.

Results A homozygous two-base pair deletion leading to premature termination and two novel TBC1D24 transcript isoforms were identified. Isoform 1 is predominant in the brain whereas isoform 2 is predominant in non-neural tissues, except for muscle.

Conclusions The very severe phenotype in our patients can be attributed to mutation severity; however, the mutation does not affect isoform 2, whereas the three previously reported mutations do. These findings expand the spectrum of the TBC1D24 mutation phenotype and the transcript isoforms.