Genetic Study of Early Onset Parkinson’s Disease in Cyprus
Abstract
:1. Introduction
2. Results
2.1. Cohort Description
2.2. Pathogenic Variants
2.3. Variants of Uncertain Significance (VUS)
3. Discussion
4. Materials and Methods
4.1. Participants
4.2. Genetic Analysis
4.2.1. DNA Sequencing
4.2.2. Detection of Copy Number Variation (CNV)
4.3. In Silico Predictions
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Case No. | RefSeq Gene | Sequence Variant | Copy Number Variant | AOO | Gender | Known Family History of Disease | Affected Family Member, AOO |
---|---|---|---|---|---|---|---|
1 | PINK1 1 | c.889del | _ | 46 | F | Yes | dizygotic twin sister, 23 |
p.(Asp297Metfs*22) (hom) | |||||||
2 | PINK1 1 | c.889del | _ | 23 | F | Yes | dizygotic twin sister, 46 |
p.(Asp297Metfs*22) (hom) | |||||||
3 | PINK1 1 | c.889del | _ | 41 | F | No | _ |
p.(Asp297Metfs*22) (hom) | |||||||
4 | PINK1 1 | c.889del | _ | 50 | F | Yes | father, unk |
p.(Asp297Metfs*22) (het) | |||||||
5 | PINK1 1 | c.889del | _ | 43 | M | No | _ |
p.(Asp297Metfs*22) (het) | |||||||
6 | PRKN 2 | _ | Ex3–4del (hom) | 45 | M | Yes | grandmother, unk |
7 | PRKN 2 | _ | Ex2del (het); Ex2–4del (het) | 50 | F | Yes | sister, 56 |
8 | PRKN 2 | _ | Ex2del (het); Ex5del (het) | 35 | M | No | _ |
9 | PRKN 2 | _ | Ex3–4del (het); Ex6–7del (het) | 50 | F | Yes | father, unk |
Case No. | RefSeq Gene | Clinical Symptoms at Onset | MDS-UPDRS Score Total (Parts I, II, III, IV) | H & Y | Years After Onset 3 | Dyskinesia | Surgery | Other Diseases, AOO |
---|---|---|---|---|---|---|---|---|
1 | PINK1 1 | R, B | 16 | 1 | 20 | No | No | hypothyroidism, 59; |
(1, 4, 11, 0) | hypertension, unk; | |||||||
2 | PINK1 1 | T, PI | 189 | 5 | 44 | Yes | No | dysarthria, 54; |
cognitive decline, 54; | ||||||||
(34, 45, 99, 11) | depression, unk | |||||||
3 | PINK1 1 | T, R, PI | 111 | 5 | 35 | Yes | STN DBS | dementia, 80; |
depression, 41; | ||||||||
(23, 28, 60, 0) | arrhythmia, unk; | |||||||
hypertension, unk | ||||||||
4 | PINK1 1 | R, B | 36 | 1 | 12 | No | No | _ |
(14, 10, 11, 1) | ||||||||
5 | PINK1 1 | R, B | 94 | 3 | 23 | Yes | STN DBS | benign prostatic hyperplasia, unk |
(13, 31, 38, 12) | ||||||||
6 | PRKN 2 | T, R, B | 76 | 3 | 24 | Yes | No | colon cancer, 75; |
skin melanoma with lung/liver metastasis, 70; | ||||||||
depression, 55; | ||||||||
(18, 14, 36, 8) | memory disturbances, 55; | |||||||
CVD, unk; | ||||||||
hypertension, unk | ||||||||
7 | PRKN 2 | T | 43 | 2 | 11 | Yes | No | sleep disturbances, 68; |
breast cancer, 56; | ||||||||
depression, 50; | ||||||||
(19, 11, 13, 0) | hypertension, 41; | |||||||
diabetes, unk | ||||||||
8 | PRKN 2 | R, B | 22 | 1 | 3 | Yes | No | bipolar disorder, 41; |
(8, 3, 11, 0) | depression, 33 | |||||||
9 | PRKN 2 | R | 43 | 1 | 13 | No | No | hypercholesterolemia, unk |
(8, 7, 28, 0) | hypertension, unk |
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Abu Manneh, R.; Chairta, P.P.; Mitsi, E.; Loizidou, M.A.; Georgiou, A.N.; Christou, Y.P.; Pantzaris, M.; Zamba-Papanicolaou, E.; Hadjisavvas, A. Genetic Study of Early Onset Parkinson’s Disease in Cyprus. Int. J. Mol. Sci. 2022, 23, 15369. https://doi.org/10.3390/ijms232315369
Abu Manneh R, Chairta PP, Mitsi E, Loizidou MA, Georgiou AN, Christou YP, Pantzaris M, Zamba-Papanicolaou E, Hadjisavvas A. Genetic Study of Early Onset Parkinson’s Disease in Cyprus. International Journal of Molecular Sciences. 2022; 23(23):15369. https://doi.org/10.3390/ijms232315369
Chicago/Turabian StyleAbu Manneh, Rana, Paraskevi P. Chairta, Ellie Mitsi, Maria A. Loizidou, Andrea N. Georgiou, Yiolanda P. Christou, Marios Pantzaris, Eleni Zamba-Papanicolaou, and Andreas Hadjisavvas. 2022. "Genetic Study of Early Onset Parkinson’s Disease in Cyprus" International Journal of Molecular Sciences 23, no. 23: 15369. https://doi.org/10.3390/ijms232315369