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P2‐120: UPDATE ON RARE SORTILIN RELATED RECEPTOR‐1 (SORL1) MUTATIONS IN KOREAN, THAI AND MALAYSIAN EOAD AND DEMENTIA PATIENTS, WITH STRUCTURE PREDICTIONS
Author(s) -
Bagyinszky Eva,
Van Vo Giau,
Shim Kyu Hwan,
Bagaria Jaya,
Pyun Jung Min,
Kang Min Ju,
Suh JiWon,
Youn Young Chul,
An Seong Soo,
Kim SangYun
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.2527
Subject(s) - missense mutation , biology , genetics , dementia , exome sequencing , exome , mutation , gene , disease , medicine
His163Pro, Trp165Cys, Gly209Ala, Leu226Phe, Leu232Pro, Ala285Val and Gly417Ala, whereas two mutations, Val96Phe and Glu280Lys, were identified in Malaysians siblings, and only Glu184Gly was discovered in a Thai subject. Unlike PSEN1 mutations, PSEN2mutations were a rare in EOADwith three variants only, including Arg62Cys, His169Asn, Val214Leu. In addition, we performed the biomarker analyses of limited patients in ADAM-EOAD cohort using Ab42, total-Tau and phosphorylated-Tau in CSF and Ab oligomers in blood by Multimer Detection System (MDS). The results from the biomarker analyses revealed the similar profiles of biomarker changes in CSF, decreased levels of Ab42 and elevated levels of total-Tau and phosphorylated-Tau. MDS results indicated the elevated levels of Ab oligomers in blood of EOAD patients in comparison with normal healthy control. Conclusions: Only 10% cases (n1⁄430) definite pathogenicity established, emphasizing the needs to survey variants in larger patient cohorts. Currently, additional segregation analyses in the family members, as well as targeting deep resequencing in large datasets for validating the role of the variants. Lastly, functional studies would be needed for the verification of the causalities.