Clinical and Molecular Findings in a Turkish Family Who Had a (c.869-1G>A) Splicing Variant in PSEN1 Gene with A Rare Condition: The Variant Alzheimer's Disease with Spastic Paraparesis
Küçük Resim Yok
Tarih
2022
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Bentham Science
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Background: Early-onset Alzheimer's disease (EOAD) is commonly diagnosed with an onset age of earlier than 65 years and accounts for 5–10% of all Alzheimer's disease (AD) cases. To date, although only 10-15% of familial EOAD cases have been explained, the genetic cause of the vast proportion of cases has not been explained. The variant Alzheimer's disease with spastic paraparesis (var- AD) is defined as a rare clinical entity characterized by early-onset dementia, spasticity of the lower extremities, and gait disturbance. Although the disease was first associated with variants in exon 9 of the PSEN1 gene, it was later shown that variations in other exons were also responsible for the disease. Objective: The current study aims to raise awareness of varAD, which occurs as a rare phenotype due to pathogenic variants in PSEN1. In addition, we aimed to evaluate the spectrum of mutations in varAD patients identified to date. Methods: Detailed family histories and clinical data were recorded. Whole exome sequencing was performed and co-segregation analysis of the family was done by Sanger sequencing. Also, a review of the molecularly confirmed patients with (varAD) from the literature was evaluated. Results: We identified a heterozygous splicing variant (c.869-1G>A) in the PSEN1 gene, in a family with two affected individuals who present with varAD. We reported the clinical and genetic findings from the affected individuals. Conclusion: We present the detailed clinical and genetic profiles of a Turkish patient with the diagnosis of varAD together with subjects from the literature. Together, we think that the clinical characteristics and the effect of the (c.869-1G>A) variant will facilitate our understanding of the PSEN1 gene in AD pathogenesis.
Açıklama
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Anahtar Kelimeler
Alzheimer's disease, Early-onset, Familial, Presenilin 1, PSEN1, Whole exome sequencing, Dementia, Neurodegeneration, Spastic paraparesis
Kaynak
Current Alzheimer Research
WoS Q Değeri
Q4
Scopus Q Değeri
Cilt
19
Sayı
3
Künye
Doğan, M., Eröz, R., Tecellioğlu, M., Gezdirici, A., Çevik, B., & Barış, İ. (2022). Clinical and Molecular Findings in a Turkish Family Who Had a (c. 869-1G> A) Splicing Variant in PSEN1 Gene with A Rare Condition: The Variant Alzheimer's Disease with Spastic Paraparesis. Current Alzheimer Research. 19 (39, 223-235.
