D-DEMØ, a distinct phenotype caused by ATP1A3 mutations.

Prange, Lyndsey

Pratt, Milton

Herman, Kristin

Schiffmann, Raphael

Mueller, David M

McLean, Melissa

Mendez, Mary Moya

Walley, Nicole

Heinzen, Erin L

Goldstein, David

Shashi, Vandana

Hunanyan, Arsen

Pagadala, Vijay

Mikati, Mohamad A

2021-01-01T14:24:46Z

2021-01-01T14:24:46Z

2020-10

2021-01-01T14:24:44Z

Objective:To describe a phenotype caused by ATP1A3 mutations, which manifests as dystonia, dysmorphism of the face, encephalopathy with developmental delay, brain MRI abnormalities always including cerebellar hypoplasia, no hemiplegia (Ø) (D-DEMØ), and neonatal onset. Methods:Review and analysis of clinical and genetic data. Results:Patients shared the above traits and had whole-exome sequencing that showed de novo variants of the ATP1A3 gene, predicted to be disease causing and occurring in regions of the protein critical for pump function. Patient 1 (c.1079C>G, p.Thr360Arg), an 8-year-old girl, presented on day 1 of life with episodic dystonia, complex partial seizures, and facial dysmorphism. MRI of the brain revealed cerebellar hypoplasia. Patient 2 (c.420G>T, p.Gln140His), an 18-year-old man, presented on day 1 of life with hypotonia, tremor, and facial dysmorphism. He later developed dystonia. MRI of the brain revealed cerebellar hypoplasia and, later, further cerebellar volume loss (atrophy). Patient 3 (c.974G>A, Gly325Asp), a 13-year-old girl, presented on day 1 of life with tremor, episodic dystonia, and facial dysmorphism. MRI of the brain showed severe cerebellar hypoplasia. Patient 4 (c.971A>G, p.Glu324Gly), a 14-year-old boy, presented on day 1 of life with tremor, hypotonia, dystonia, nystagmus, facial dysmorphism, and later seizures. MRI of the brain revealed moderate cerebellar hypoplasia. Conclusions:D-DEMØ represents an ATP1A3-related phenotype, the observation of which should trigger investigation for ATP1A3 mutations. Our findings, and the presence of multiple distinct ATP1A3-related phenotypes, support the possibility that there are differences in the underlying mechanisms.

NG2020013383

2376-7839

2376-7839

https://hdl.handle.net/10161/21943

eng

Ovid Technologies (Wolters Kluwer Health)

Neurology. Genetics

10.1212/nxg.0000000000000466

D-DEMØ, a distinct phenotype caused by ATP1A3 mutations.

Journal article

Mikati, Mohamad A|0000-0003-0363-8715

e466

5

School of Medicine

Duke-UNC Center for Brain Imaging and Analysis

Neurobiology

Duke Science & Society

Duke Institute for Brain Sciences

Pediatrics, Neurology

Duke

Institutes and Centers

Basic Science Departments

Initiatives

Institutes and Provost's Academic Units

University Institutes and Centers

Pediatrics

Clinical Science Departments

Published

6