SCA28: Novel Mutation in the AFG3L2 Proteolytic Domain Causes a Mild Cerebellar Syndrome with Selective Type-1 Muscle Fiber Atrophy

Kirsten Svenstrup; Troels Tolstrup Nielsen; Frederik Aidt; Nina Rostgaard; Morten Duno; Flemming Wibrand; Tua Vinther-Jensen; Ian Law; John Vissing; Peter Roos; Lena Elisabeth Hjermind; Jørgen Erik Nielsen

doi:10.1007/s12311-016-0765-1

SCA28: Novel Mutation in the AFG3L2 Proteolytic Domain Causes a Mild Cerebellar Syndrome with Selective Type-1 Muscle Fiber Atrophy

Cerebellum. 2017 Feb;16(1):62-67. doi: 10.1007/s12311-016-0765-1.

Authors

Kirsten Svenstrup^{1

2

3}, Troels Tolstrup Nielsen⁴, Frederik Aidt², Nina Rostgaard⁵, Morten Duno⁶, Flemming Wibrand⁶, Tua Vinther-Jensen^{1

2}, Ian Law⁷, John Vissing³, Peter Roos¹, Lena Elisabeth Hjermind^{1

2}, Jørgen Erik Nielsen^{1

2

5}

Affiliations

¹ Danish Dementia Research Centre, Neurogenetics Clinic, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
² Department of Cellular and Molecular Medicine, Section of Neurogenetics, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
³ Copenhagen Neuromuscular Center and Clinic, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
⁴ Neurogenetics Research Laboratory, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Troels.Tolstrup.Nielsen@regionh.dk.
⁵ Neurogenetics Research Laboratory, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
⁶ Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
⁷ Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

PMID: 26868664
DOI: 10.1007/s12311-016-0765-1

Abstract

The spinocerebellar ataxias (SCA) are a group of rare inherited neurodegenerative diseases characterized by slowly progressive cerebellar ataxia, resulting in unsteady gait, clumsiness, and dysarthria. The disorders are predominantly inherited in an autosomal dominant manner. Mutations in the gene AFG3L2 that encodes a subunit of the mitochondrial m-AAA protease have previously been shown to cause spinocerebellar ataxia type 28 (SCA28). Here, we present the clinical phenotypes of three patients from a family with autosomal dominant cerebellar ataxia and show by molecular genetics and in silico modelling that this is caused by a novel missense mutation in the AFG3L2 gene. Furthermore, we show, for the first time, fluorodeoxyglucose-positron emission tomography (FDG-PET) scans of the brain and selective type I fiber atrophy of skeletal muscle of SCA28 patients indicating non-nervous-system involvement in SCA28 as well.

Keywords: ADCA; AGF3L2; FDG-PET; Muscle; SCA; SCA28.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

ATP-Dependent Proteases / genetics*
ATPases Associated with Diverse Cellular Activities
Adult
Aged
Brain / diagnostic imaging*
Brain / metabolism
Cerebellar Ataxia / diagnostic imaging
Cerebellar Ataxia / genetics*
Cerebellar Ataxia / metabolism
Cerebellar Ataxia / pathology*
Family
Female
Humans
Male
Middle Aged
Muscle Fibers, Slow-Twitch / pathology*
Mutation, Missense*
Phenotype
Protein Domains

Substances

ATP-Dependent Proteases
AFG3L2 protein, human
ATPases Associated with Diverse Cellular Activities