Mutation in Adora1 Identified As Likely Cause of Early-Onset Parkinsonism and Cognitive Dysfunction

Mutation in Adora1 Identified As Likely Cause of Early-Onset Parkinsonism and Cognitive Dysfunction Publisher Pubmed

Jaberi E¹ ; Rohani M² ; Shahidi GA² ; Nafissi S³ ; Arefian E¹ ; Soleimani M⁴ ; Moghadam A¹ ; Arzenani MK⁵ ; Keramatian F⁶ ; Klotzle B⁷ ; Fan JB⁷ ; Turk C⁷ ; Steemers F⁷ ; Elahi E^{1, 6}

Show Affiliations

1. School of Biology, College of Science, University of Tehran, Tehran, Iran
2. Department of Neurology, Hazrat Rasool Hospital, Iran University of Medical Sciences, Tehran, Iran
3. Department of Neurology, Tehran University of Medical Sciences, Tehran, Iran
4. School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
5. Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
6. Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
7. Illumina, San Diego, CA, United States

Source: Movement Disorders Published:2016

Abstract

Background: We aimed to identify the genetic cause of neurological disease in an Iranian family whose manifestations include symptoms of parkinsonism and cognitive dysfunction. Methods: Clinical data on the patients were gathered by interviews with parents, neurological examinations, and laboratory tests. Genetic analysis was performed by genome-wide single-nucleotide polymorphism homozygosity mapping and exome sequencing. The effect of putative disease-causing mutation was assessed by immunocytochemistry on HEK293 cells and Western blotting on proteins extracted from HEK293 cells transfected with wild-type and mutated genes. Results: Homozygosity mapping and exome sequencing led to identification of a mutation in ADORA1 that causes p.Gly279Ser in the encoded protein, adenosine A1 receptor (A1R), as the probable cause of disease. The mutation segregated with disease status in the family, affects a highly conserved amino acid, and was absent in 700 controls. Conclusions: The known biological activities of A1R in brain functions including its physical interaction with and inhibitory effect on dopamine receptor D1 provide supportive evidence that disruptions of A1R may result in neurological dysfunction. Also, recent evidence on the related adenosine A2B receptor marks the domain in which the mutation is positioned as important for function. Finally, ADORA1 is located within the Parkinson's disease locus PARK16, which has been identified in several populations. ADORA1 may be the PD susceptibility gene within this locus. The molecular mechanism by which p.Gly279Ser disrupts A1R function remains unknown, but a quantitative effect on interaction with the dopamine receptor was not shown. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society

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Style	Citing Format
MLA	Jaberi E, et al.. "Mutation in Adora1 Identified As Likely Cause of Early-Onset Parkinsonism and Cognitive Dysfunction." Movement Disorders, vol. 31, no. 7, 2016, pp. 1004-1011.
APA	Jaberi E, Rohani M, Shahidi GA, Nafissi S, Arefian E, Soleimani M, Moghadam A, Arzenani MK, Keramatian F, Klotzle B, Fan JB, Turk C, Steemers F, Elahi E (2016). Mutation in Adora1 Identified As Likely Cause of Early-Onset Parkinsonism and Cognitive Dysfunction. Movement Disorders, 31(7), 1004-1011.
Chicago	Jaberi E, Rohani M, Shahidi GA, Nafissi S, Arefian E, Soleimani M, Moghadam A, et al.. "Mutation in Adora1 Identified As Likely Cause of Early-Onset Parkinsonism and Cognitive Dysfunction." Movement Disorders 31, no. 7 (2016): 1004-1011.
Harvard	Jaberi E et al. (2016) 'Mutation in Adora1 Identified As Likely Cause of Early-Onset Parkinsonism and Cognitive Dysfunction', Movement Disorders, 31(7), pp. 1004-1011.
Vancouver	Jaberi E, Rohani M, Shahidi GA, Nafissi S, Arefian E, Soleimani M, et al.. Mutation in Adora1 Identified As Likely Cause of Early-Onset Parkinsonism and Cognitive Dysfunction. Movement Disorders. 2016;31(7):1004-1011.
BibTex	@article{ author = {Jaberi E and Rohani M and Shahidi GA and Nafissi S and Arefian E and Soleimani M and Moghadam A and Arzenani MK and Keramatian F and Klotzle B and Fan JB and Turk C and Steemers F and Elahi E}, title = {Mutation in Adora1 Identified As Likely Cause of Early-Onset Parkinsonism and Cognitive Dysfunction}, journal = {Movement Disorders}, volume = {31}, number = {7}, pages = {1004-1011}, year = {2016} }
RIS	TY - JOUR AU - Jaberi E AU - Rohani M AU - Shahidi GA AU - Nafissi S AU - Arefian E AU - Soleimani M AU - Moghadam A AU - Arzenani MK AU - Keramatian F AU - Klotzle B AU - Fan JB AU - Turk C AU - Steemers F AU - Elahi E TI - Mutation in Adora1 Identified As Likely Cause of Early-Onset Parkinsonism and Cognitive Dysfunction JO - Movement Disorders VL - 31 IS - 7 SP - 1004 EP - 1011 PY - 2016 ER -

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