PMC6079244_01
PMC6079244_02
(A) Pedigrees for the family and haplotype construction. Filled circles indicate patient. Arrows point to the probands for the family. Haplotypes are displayed below the symbols of the family members available for analysis. Markers used in the haplotype construction are listed on the left. Black bars depict the paternal disease haplotype; hatched bars, the disease haplotype of the mother; and open bars, the haplotypes that do not contain a variant. Wt denotes the wild-type allele. (B) Sanger sequencing. The members of the family are listed on the left. Left-pointing arrows denote the forward sequence of c.1416_1437del (p.Ser473Argfs*43) in TBC1D24. Right-pointing arrows indicate the forward sequence of c.1499C>T (p.Ala500Val) in TBC1D24. Arrow indicates the locations of the mutations. (C) Domain information for the protein encoded by the TBC1D24 gene. Arrows indicate the locations of the mutation (p.Ser473Argfs*43) and the premature stop codon introduced by the deletion mutation. The wild-type TBC1D24 protein has 559 amino acids. It contains both the Rab GTPase domain (purple) and TLDc domain (blue). The mutation p.Ser473Argfs*43 is predicted to delete 45 amino acids from the C terminus of the TBC1D24 protein.
fneur-09-00623-g0001.jpg
PMC6079244_02_fneur-09-00623-g0001.jpg
F1
Sanger sequencing, respectively: c.1416_1437del (p.Ser473Argfs*43) and c.1499C>T (p.Ala500Val; Figure 1B). It is further predicted to introduce a premature stop codon at position 514, thereby truncating 45 amino acids at the C terminus of the TBC1D24 protein (ORF Finder predicted; Figure 1C).
24 h-EEG monitoring indicated non-convulsive status epilepticus. (A,B) Predominant theta and delta activity in bilateral hemispheres. With the increase in voltage from 30 to 485 muV, the frequency decreased from 6 to 2.5 Hz. (C) The frequency of beta activity increased while theta activity decreased 1 min following intravenous injection of diazepam. (D) Beta activity were bilaterally predominant nearly 1 hr following injection. (E) At about 1.5 h after intravenous injection of diazepam, the EEG recovered to normal background (majority beta activity with maximum amplitudes ranged from 18.5 to 30.5 muV at frequencies of 5-30 Hz, scattered theta with maximum amplitudes ranged from 20 to 40 muV at frequencies of 5-7.5 Hz). By this time, the patient's crying subsided, her vision recovered, and she could answer questions as usual.
fneur-09-00623-g0002.jpg
PMC6079244_02_fneur-09-00623-g0002.jpg
F2
With the increase in voltage from 30 to 485 muV, the frequency decreased from 6 to 2.5 Hz. (Figures 2A,B). The phenomenon acutely abolished after intravenous injection of diazepam and frequency of beta activity increased and finally recovered to normal EEG background (Figure 2D). Our legend of Figure 2 further includes all relevant details.
Cranial MRI showed mild atrophic changes in bilateral hemisphere and cerebellum. Ventricular systems were generally enlarged. Cerebral sulcus and fissures widened in bilateral hemisphere and cerebellum. Long arrowheads in Figure (A,B,D) showed widened sulcus and fissures in hemisphere and cerebellum. Short arrowheads in (B,C) showed enlarged the fourth ventricle and cisterna magna.
fneur-09-00623-g0003.jpg
PMC6079244_02_fneur-09-00623-g0003.jpg
F3
Analysis of the imaging revealed mild atrophic changes in both hemispheres, as well as the cerebellum (Figure 3).