Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2020 Jun 1;143(6):e49.
doi: 10.1093/brain/awaa120.

A homozygous GDAP2 loss-of-function variant in a patient with adult-onset cerebellar ataxia

Affiliations
Comment

A homozygous GDAP2 loss-of-function variant in a patient with adult-onset cerebellar ataxia

Marianthi Breza et al. Brain. .
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Genetic and neuroimaging findings of this case: (A) Family pedigree. (B) Validation of the variant identified (c.134del, p.Pro45Leufs*22) by Sanger sequencing as homozygous in the patient and heterozygous in the mother compared to a control reference. (CJ) Brain MRI findings of this case. (C) Sagittal T2-weighted sequence showing cerebellar atrophy, midbrain and pons atrophy (hummingbird sign), and thinning of corpus callosum. (D and E) Coronal and axial T1-weighted sequence. Cerebellar atrophy is noted particularly in upper and central cerebellar vermis, however cortical atrophy, and dilated fissures (Global Cortical Atrophy, GCA scale: 2) were also present. (F and G) Axial T2-weighted and SWI (susceptibility weighted imaging) sequences showing lentiform hemosiderin depositions. (HJ) Magnetic resonance tractography using diffusion tensor imaging shows no significant alterations in the reconstructed corticospinal and cerebellar tracts superimposed on anatomical 3D T1-weighted images in axial, coronal and sagittal planes. L = left; R = right; LH = left hemisphere; RH = right hemisphere. [K(i and ii)] Patient’s ASL (arterial spin labelling) representative colour-coded images at cerebellar and lateral ventricles level showing reduced perfusion in cerebellum and in cerebral cortex. [K(iii and iv)] Control ASL representative colour coded images at cerebellar and lateral ventricles level. (L) Homozygosity mapping showing homozygous segments on chromosome 1 where the variant identified resides within a 3.1 Mb homozygous chromosomal segment (ch1: 114 522 285–117 628 869).

Comment in

Comment on

References

    1. Aken BL, Ayling S, Barrell D, Clarke L, Curwen V, Fairley S, et al.The Ensembl gene annotation system. Database (Oxford) 2016; 1–19. - PMC - PubMed
    1. Eidhof I, Baets J, Kamsteeg EJ, Deconinck T, van Ninhuijs L, Martin JJ, et al.GDAP2 mutations implicate susceptibility to cellular stress in a new form of cerebellar ataxia. Brain 2018; 141: 2592–604. - PMC - PubMed
    1. Gonzalez Esquivel D, Ramirez-Ortega D, Pineda B, Castro N, Rios C, Perez de la Cruz V.. Kynurenine pathway metabolites and enzymes involved in redox reactions. Neuropharmacology 2017; 112: 331–45. - PubMed
    1. Han W, Li X, Fu X.. The macro domain protein family: structure, functions, and their potential therapeutic implications. Mutat Res 2011; 727: 86–103. - PMC - PubMed
    1. Karras GI, Kustatscher G, Buhecha HR, Allen MD, Pugieux C, Sait F, et al.The macro domain is an ADP-ribose binding module. EMBO J 2005; 24: 1911–20. - PMC - PubMed