PMC10149840_01
T2-weighted brain MRI showing the "eye-of-the-tiger" sign.
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F1
T2-weighted brain magnetic resonance imaging (MRI) showed a characteristic of the "eye-of-the-tiger" sign (Figure 1).
(A) Family with compound heterozygous PANK2 gene variants. Proband PKAN is indicated with an arrow. (B) Amino acid sequence alignment between species and PANK family proteins, the red font indicates amino acid changes previously reported in PKAN.
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F2
Thr498Ser variant (Figure 2A). These two variants were absent in 1,000 g, ExAC, and gnomAD databases. Amino acid sequence alignment shows that Ile501 and Thr498 are highly conserved both across species and in PANK family proteins (Figure 2B). Ile501Asn has been reported in several previous studies, while Thr498Ser was novel. According to the ACMG standard, PANK2 p.Ile501Asn was classified as likely pathogenic (PS1, PM1, PM2, and PP3), while PANK2 p.Thr498Ser was classified as a variant of uncertain significance (PM1, PM2, and PP3).