Title: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
Volume: 19
Issue: 3
Author(s): Mustafa Doğan*, Recep Eröz, Mehmet Tecellioğlu, Alper Gezdirici, Betül Çevik and İbrahim Barış
Affiliation:
- Department of Medical Genetics, Malatya Turgut Ozal University Medical Faculty, Malatya, Turkey
Keywords:
Alzheimer's disease, Early-onset, familial, presenilin 1, PSEN1, whole exome sequencing, dementia, neurodegeneration, spastic paraparesis
Abstract:
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.
