De novo VPS16 missense variant causes infantile-onset dystonia with defective autophagic flux
Enrique Gonzalez Saez-Diez, Xutong Xue, Amy Tam, Hyo-Min Kim, Siofra Carty, Joshua Rong, Monica Ferrer-Socorro, Kathryn Yang, Darius Ebrahimi-Fakhari
Enrique Gonzalez Saez-Diez, Xutong Xue, Amy Tam, Hyo-Min Kim, Siofra Carty, Joshua Rong, Monica Ferrer-Socorro, Kathryn Yang, Darius Ebrahimi-Fakhari
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Research Letter Genetics Neuroscience

De novo VPS16 missense variant causes infantile-onset dystonia with defective autophagic flux

Abstract

Authors

Enrique Gonzalez Saez-Diez, Xutong Xue, Amy Tam, Hyo-Min Kim, Siofra Carty, Joshua Rong, Monica Ferrer-Socorro, Kathryn Yang, Darius Ebrahimi-Fakhari

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Figure 1

De novo VPS16 missense variant p.Ala466Thr causes caudate atrophy and impaired autophagic flux in patient-derived fibroblasts.

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De novo VPS16 missense variant p.Ala466Thr causes caudate atrophy and im...
(A and B) Brain MRI demonstrating symmetric, caudate-predominant striatal volume loss with ex vacuo dilatation of the frontal horns (A, T1-weighted axial; B, T2-weighted axial). No T2 signal abnormality, mineralization, or putaminal involvement is present. (C and D) Transmission electron micrographs of control (C) and patient (D) skin fibroblasts. Yellow dashed circles in D mark enlarged vacuolar structures consistent with stalled autolysosomes, absent in control cells. Scale bars: 1 μm. (E) Representative immunoblots for p62/SQSTM1, LC3B (LC3-I and LC3-II), and β-actin (loading control) in control and patient fibroblasts. (F) Quantification of p62 protein levels normalized to β-actin (n = 3 biological replicates). *P < 0.05, unpaired t test. (G) Quantification of the LC3-II/LC3-I ratio (n = 3 biological replicates). *P < 0.05, unpaired t test. Data presented as violin plots with individual data points.