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

Dogan M., ERÖZ R., TECELLİOĞLU M., Gezdirici A., ÇEVİK B., Baris I.

CURRENT ALZHEIMER RESEARCH, cilt.19, sa.3, ss.223-235, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 19 Sayı: 3
  • Basım Tarihi: 2022
  • Doi Numarası: 10.2174/1567205019666220414101251
  • Dergi Adı: CURRENT ALZHEIMER RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Abstracts in Social Gerontology, Chemical Abstracts Core, EMBASE, MEDLINE, Psycinfo
  • Sayfa Sayıları: ss.223-235
  • Anahtar Kelimeler: Alzheimer's disease, Early-onset, familial, presenilin 1, PSEN1, whole exome sequencing, dementia, neurodegeneration, spastic paraparesis, COTTON WOOL PLAQUES, PRESENILIN-1 MUTATION, AMYLOID HYPOTHESIS, BETA PEPTIDE, ONSET, DELETION, DEMENTIA, PATIENT, EXON-9, ASSOCIATION
  • İnönü Üniversitesi Adresli: Evet

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 (varAD) 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.