PSEN1 p.Thr116Ile Variant in Two Korean Families with Young Onset Alzheimer’s Disease
Abstract
:1. Introduction
2. Results
2.1. Genetic Analysis
2.2. In Silico Predictions and 3D Modeling
3. Discussion
4. Materials and Methods
4.1. AD Patients and Their Families
4.1.1. Family 1
4.1.2. Family 2
4.2. Genetic Analysis
4.3. Single Strand Conformation Polymorphism (SSCP)
4.4. In Silico Screening and Structure Predictions
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Case | First Case | Second Case | Third Case | Korean-1 | Korean-2 |
---|---|---|---|---|---|
Country | Italy | France | France | Korea | Korea |
Age of onset (years) | 45 years | 40–47 years | 38–44 years | 41 years | 38 years |
Disease | EOAD | EOAD | EOAD | EOAD | EOAD |
Imaging | Atrophy and fronto-parieto-temporal enlargement of cortical sulci | NA | NA | MRI: atrophy in the right temporal and parietal regions PET: NA | MRI: Atrophy in the medial region PET: reduced metabolism in temporal and parietal region |
MMSE | 14/30 | NA | NA | Initially 24/30, later 18/30 | 23/30 |
Clinical phenotype | Memory loss, confusion and disorientation, followed by progressive memory loss | No detailed information, but patients fulfilled the NINCDS-ADRDA criteria | No detailed information | Memory impairment, confusion, visuospatial dysfunction, speech disturbances. | Impairment in memory and mood, marked ideomotor apraxia |
Family history | Unknown | Familial | Probable familial | Familial | Familial |
References | [12] | [13] | [14] | Our data | Our data [11] |
Mutation | Thr116Asn | Thr116Ile |
---|---|---|
Pathogenicity | Pathogenic | Pathogenic |
Age of onset | 35–41 years (Familial) | 40–47 years (Familial and de novo) |
Clinical phenotype | EOAD (no clinical data) | EOAD |
PolyPhen2 scores (HumDiv) | 1.00 (probably damaging) | 1.00 (probably damaging) |
SIFT scores | 0 (damaging) | 0.07 (tolerated) |
References | [12,13,14] | [15] |
Mutation | Dx | Clinical Symptoms/Pathology | Age of Onset | Family History | Functional Studies | References |
---|---|---|---|---|---|---|
Phe105Cys | AD | Memory impairment and behavioral changes | 45–60 years | Positive | NA | [28] |
Phe105Ile | AD | NA | 53–58 years | Positive | NA | [19] |
Ple105Leu | AD | Parkinson’s like symptoms, severe dementia | 52 years | Probable positive | NA | [18] |
Arg108Gln | AD | Progressive cognitive decline, myoclonic jerks | 45 years | Segregation could not proven | NA | [17] |
L113_I114insT | AD | Postmortem studies confirmed the AD | 34–45 years | Familial | 3.4-fold higher Aβ42 levels | [16] |
Leu113Pro | FTD | Behavioral impairments, myoclonic jerks, seizures | 38–50 years | Familial | NA | [19] |
Leu113Gln | AD | Rapid progressive dementia, drop attacks, myoclonic seizures, and bilateral spasticity. | 33–36 years | Familial | NA | [18] |
Tyr115Cys | AD | Postmortem studies confirmed the AD | 39–45 years | Familial | 5.4-fold higher Aβ42 levels | [21] |
Tyr115His | AD | Epileptic seizure, myoclonus | 35–40 years | Familial | Increased levels of Aβ42, lower Aβ40 | [29] |
Thr116Ile | Was discussed in details in Table 1 and Table 2 | |||||
Thr116Asn | ||||||
Pro117Ala | AD | Issues with balance, tremor, ataxia | 29–35 years | Familial | Elevated Aβ42/40 ratio | [23] |
Pro117Leu | AD | Progressive memory impairment, mood swings, seizure, myoclonus | 24–33 years | Familial/de novo | Elevated Aβ42, inhibited neural overgrowth | [20] |
Pro117Arg | AD | Apathy, behavioral changes, seizures, myoclonus, gait impairment | 33–36 years | Unknown/ familial | Elevated total Aβ | [30] |
Pro117Ser | AD | Personality changes, severe dementia, seizures, myoclonus, tremor | 29–33 years | Familial | Elevated Aβ42 levels | [31] |
Glu120Asp | AD | Language impairment, seizures, disorientation | 34–53 years | Familial | NA | [22] |
Glu120Gly | AD | Memory and cognitive decline, seizure, gait disturbances | 30–39 years | Familial | NA | [32] |
Glu120Lys | AD | Spastic paraparesis | 43–45 years | Familial/ unknown | Elevated Aβ42/40 ratio | [33,34] |
Glu123Lys | AD | Progressive aphasia, reduced visuospatial activity | 56–62 years | Familial | NA | [24] |
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Bagyinszky, E.; Lee, H.-M.; Van Giau, V.; Koh, S.-B.; Jeong, J.H.; An, S.S.A.; Kim, S. PSEN1 p.Thr116Ile Variant in Two Korean Families with Young Onset Alzheimer’s Disease. Int. J. Mol. Sci. 2018, 19, 2604. https://doi.org/10.3390/ijms19092604
Bagyinszky E, Lee H-M, Van Giau V, Koh S-B, Jeong JH, An SSA, Kim S. PSEN1 p.Thr116Ile Variant in Two Korean Families with Young Onset Alzheimer’s Disease. International Journal of Molecular Sciences. 2018; 19(9):2604. https://doi.org/10.3390/ijms19092604
Chicago/Turabian StyleBagyinszky, Eva, Hye-Mi Lee, Vo Van Giau, Seong-Beom Koh, Jee Hyang Jeong, Seong Soo A. An, and SangYun Kim. 2018. "PSEN1 p.Thr116Ile Variant in Two Korean Families with Young Onset Alzheimer’s Disease" International Journal of Molecular Sciences 19, no. 9: 2604. https://doi.org/10.3390/ijms19092604