New mutation in the PSEN1 (E120G) gene associated with early onset Alzheimer's disease

Abstract

Objective To describe a novel mutation in exon 5 of the presenilin 1 gene (E120G) associated with early-onset autosomal dominant Alzheimer's disease (AD). Patient and methods The proband was a man who began with memory loss and progressive cognitive decline at the age of 34. His father and his sister suffered from early-onset cognitive decline. The genetic study performed on the blood sample using the single strand conformation polymorphism (SSCP) technique did not detect any abnormality suggestive of the presence of a mutation in PSEN1, PSEN2, and APP. In the last stage of the disease the patient had seizures and gait alteration. He died at the age of 44. Coding exons 3–12 of PSEN1 were studied by direct sequencing using isolated DNA from frozen brain tissue of the proband. Results The neuropathological examination showed the presence of frequent amyloid plaques and neurofi brillary tangles and severe amyloid angiopathy. The direct sequencing of the PSEN1 gene disclosed the presence of the E120G mutation. Conclusions E120G is a novel mutation in PSEN1 that probably causes early-onset autosomal dominant AD. Absence of genetic alterations in screening techniques (SSCP) does not rule out the presence of mutations. We recommend direct sequencing for the genetic study of patients with early-onset autosomal dominant AD.