PMC9896164_01
PMC9896164_02
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Brain MRI of the affected patient showing evidence of a molar tooth sign (a, T1WI; b, T2WI), dysplastic cerebellar vermis (c, T1WI; d, T2WI), and the typical "bat wing" morphology (e, T2WI; f, T2 fluid-attenuated inversion recovery sequence axial MRI).
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Cerebral magnetic resonance imaging (MRI) examinations showed a molar tooth sign (Figure 1a and b). Figure 1c and d show the widened extracerebral spaces of bilateral temporal lobes and poor continuity of cerebellar hemispheres. The fourth ventricle gave rise to the batwing appearance (Figure 1e and f).
PMC9896164_04
Sanger sequencing suggesting the proband and his mother were heterozygous for CPLANE1 c.8948dupT (p.P2984Tfs*7) variant (a), and the proband and his father were heterozygous for CPLANE1 c.247 G > T (p.G83X) variant (b).
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WES and Sanger sequencing detected two compound heterozygous variants of CPLANE1 (NM_023073): c.8948dupT (p.P2984Tfs*7) (Figure 2a) and c.247G > T (p.G83X) (Figure 2b).
A pedigree of the family studied in this study. V1, c.8948dupT (p.P2984Tfs*7); V2, c.247 G > T (p.G83X). Circles, females; Squares, males. The black square presented the proband.
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Sanger sequencing confirmed that c.8948dupT (p.P2984Tfs*7) was of maternal origin, and c.247G > T (p.G83X) was paternally inherited, which was depicted in the pedigrees (Figure 3).
Multiple sequences alignment depiction of CPLANE1 gene. The red boxes represent the mutant sites p.G83X and p.P2984Tfs*7.
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CPLANE1 c.8948dupT and c.247G > T variants occurred within the conserved protein sequences (Figure 4). Conserved domain analysis revealed that the function of JBTS-associated domain is still unconfirmed. Figure 4 shows the alignment of multiple CPLANE1 sequences.