PMC8077499_01
a, b Video-electroencephalogram (EEG) at the age of 29. a The EEG shows generalized bursts of sharp waves with conjugate deviation and laughing on the monitor. b Longitudinal bipolar montage. Even after the convulsion stopped and the patient closed her eyes, the focal spikes with phase reversal at the right middle temporal region continue, and then slowly disappear (not shown). c Follow-up EEG taken at the age of 34 shows a slight slowing of the background activity without any obvious spikes.
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F1
Video-electroencephalogram (EEG) at the age of 29 showed generalized bursts of sharp waves with conjugate deviation and involuntary laughing on the monitor (Fig. 1a). The epileptiform discharges slowly subsided after the convulsion stopped and she closed her eyes (Fig. 1b). Follow-up EEG showed disappearance of epileptiform discharges (Fig. 1c).
a Brain magnetic resonance imaging (MRI) at the age of 34 shows frontal lobe-dominant atrophy with dilation of the ventricles and hyperintensity of periventricular white matter on T2-weighted image. b T1-weighted image shows cerebellar atrophy in the sagittal plane. c Images of cerebral blood flow single-photon emission computed tomography using N-isopropyl-p-[123I] iodoamphetamine (IMP-SPECT) at the age of 34. The Z-score is higher as the degree of decrease in cerebral blood flow is larger than that of an age-matched normal database. IMP-SPECT reveals significant hypoperfusion in the frontal lobe excluding the motor area and cerebellum. LT, left; LAT, lateral; MED, medial; RT, right.
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F2
At that time, brain magnetic resonance imaging (MRI) showed frontal lobe-dominant cerebral atrophy and whole cerebellar atrophy with high intensity in periventricular white matter on T2-weighted images (Fig. 2a, b). The cerebellum also showed hypoperfusion (Fig. 2c).
Sequencing analysis of the patient. Sequencing shows a homozygous missense mutation in the NHLRC1 gene (p. W219R), with a single nucleotide exchange (T-to-C) in exon 1 of the NHLRC1 gene.
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F3
We identified a W219R homozygous mutation in exon 1 of the NHLRC1 gene using next-gene sequencing (Illumina MinSeq-based method and VariantStudio analysis) and genomic DNA extracted from her white blood cells (Fig. 3).