NDLI: A Novel Frameshift Mutation in the AFG3L2 Gene in a Patient with Spinocerebellar Ataxia

Content Provider	Springer Nature Link
Author	Musova, Zuzana Kaiserova, Michaela Kriegova, Eva Fillerova, Regina Vasovcak, Peter Santava, Alena Mensikova, Katerina Zumrova, Alena Krepelova, Anna Sedlacek, Zdenek Kanovsky, Petr
Copyright Year	2013
Abstract	Spinocerebellar ataxia type 28 (SCA28) is an autosomal dominant neurodegenerative disorder caused by missense AFG3L2 mutations. To examine the occurrence of SCA28 in the Czech Republic, we screened 288 unrelated ataxic patients with hereditary (N = 49) and sporadic or unknown (N = 239) form of ataxia for mutations in exons 15 and 16, the AFG3L2 mutation hotspots. A single significant variant, frameshift mutation c.1958dupT leading to a premature termination codon, was identified in a patient with slowly progressive speech and gait problems starting at the age of 68 years. Neurological examination showed cerebellar ataxia, mild Parkinsonian features with predominant bradykinesia, polyneuropathy of the lower limbs, and cognitive decline. However, other common SCA28 features like pyramidal tract signs (lower limb hyperreflexia, positive Babinski sign), ophthalmoparesis or ptosis were absent. The mutation was also found in a patient’s unaffected daughter in whom a targeted examination at 53 years of age revealed mild imbalance signs. RNA analysis showed a decreased ratio of the transcript from the mutated AFG3L2 allele relative to the normal transcript in the peripheral lymphocytes of both patients. The ratio was increased by puromycin treatment, indicating that the mutated transcript can be degraded via nonsense-mediated RNA decay. The causal link between the mutation and the phenotype of the patient is currently unclear but a pathogenic mechanism based on AFG3L2 haploinsufficiency rather than the usual dominant-negative effect of missense AFG3L2 mutations reported in SCA28, cannot be excluded.
Starting Page	331
Ending Page	337
Page Count	7
File Format	PDF
ISSN	14734222
Journal	The Cerebellum
Volume Number	13
Issue Number	3
e-ISSN	14734230
Language	English
Publisher	Springer US
Publisher Date	2013-11-23
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	SCA28 Spinocerebellar ataxia AFG3L2 Frameshift mutation Neurosciences Neurology Neurobiology
Content Type	Text
Resource Type	Article
Subject	Neurology Neurology (clinical)

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

A Novel Missense Mutation in AFG3L2 Associated with Late Onset and Slow Progression of Spinocerebellar Ataxia Type 28

Neurocognitive Characterization of an SCA28 Family Caused by a Novel AFG3L2 Gene Mutation

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

Spinocerebellar ataxia type 28: A novel autosomal dominant cerebellar ataxia characterized by slow progression and ophthalmoparesis

A Novel TTBK2 De Novo Mutation in a Danish Family with Early-Onset Spinocerebellar Ataxia

Spinocerebellar ataxia 28: a novel AFG3L2 mutation in a German family with young onset, slow progression and saccadic slowing

A Family with Spinocerebellar Ataxia Type 5 Found to Have a Novel Missense Mutation within a SPTBN2 Spectrin Repeat

Early onset and slow progression of SCA28, a rare dominant ataxia in a large four-generation family with a novel AFG3L2 mutation

Origin of the Spinocerebellar Ataxia Type 7 Gene Mutation in Mexican Population

A Novel Frameshift Mutation in the AFG3L2 Gene in a Patient with Spinocerebellar Ataxia

Similar Documents

A Novel Missense Mutation in AFG3L2 Associated with Late Onset and Slow Progression of Spinocerebellar Ataxia Type 28

Neurocognitive Characterization of an SCA28 Family Caused by a Novel AFG3L2 Gene Mutation

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

Spinocerebellar ataxia type 28: A novel autosomal dominant cerebellar ataxia characterized by slow progression and ophthalmoparesis

A Novel TTBK2 De Novo Mutation in a Danish Family with Early-Onset Spinocerebellar Ataxia

Spinocerebellar ataxia 28: a novel AFG3L2 mutation in a German family with young onset, slow progression and saccadic slowing

A Family with Spinocerebellar Ataxia Type 5 Found to Have a Novel Missense Mutation within a SPTBN2 Spectrin Repeat

Early onset and slow progression of SCA28, a rare dominant ataxia in a large four-generation family with a novel AFG3L2 mutation

Origin of the Spinocerebellar Ataxia Type 7 Gene Mutation in Mexican Population

A Novel Frameshift Mutation in the AFG3L2 Gene in a Patient with Spinocerebellar Ataxia