To investigate the etiology of early-onset Alzheimer disease which caused by presenilin 1 (PSEN1) mutation in one case of early-onset Alzheimer disease patient with initial symptom of epilepsy childhood and his large family.

From November 28, 2014 to November 14, 2015, one case of patient with initial symptom of epilepsy from age of 12 years old who was diagnosed as early-onset Alzheimer disease (the proband) in Department of Neurology of Peking University First Hospital and his large family genealogy (Ⅰ-Ⅳ generations)were recruited as research objects. Diagnostic criteria of Alzheimer disease were as follows. ①Age of onset less than 65 years old. ②The clinical examination evidence supported the diagnosis for dementia; ③Cognitive impairment showed in more than two fields. ④The progressive decline of memory and with other cognitive disorders. ⑤Without disturbance of consciousness. ⑥Without other systemic diseases and the memory and cognitive impairment which can be explained by the brain diseases. The proband, a male, 36 years old had seizures from the age of 12-year-old. He visited the hospital to seek for etiological and to study for his abnormal family history. Clinical data and genomic DNA of the proband and his family members were collected. Targeted next-generation sequencing (TGS) was performed to detect the PSEN1 mutation in the proband. All exons and exon-intron boundaries of PSEN1 were checked by polymerase chain reaction (PCR). Sanger sequencing was used to verify the corresponding mutation. The procedure of this study was consistent with ethical standard established by the committee of investigation in human beings of Peking University First Hospital. And it was approved by this committee. Informed consent was obtained from all participants.

①The proband (Ⅲ₁₆) presented with seizures when he was 12 years old. After treated by sodium valproate from the age of 15 years old, the seizure was not observed. He had normal psychomotor development. His cranial MRI showed no abnormality. Relapse occurred when he stopped the drug at the age of 33 years old and sodium valproate remained effective. Primary epilepsy was suspected. However, he have presented with memory loss and disorientation since the age of 35 years old. ②His grandmother (Ⅰ₂) had psychiatric disorder in her thirties and died at around 40 years old. His father (Ⅱ₆), two aunts(Ⅱ₄and Ⅱ₅)and two uncles(Ⅱ₂and Ⅱ₃) presented with similar symptoms, progressive memory loss and mental retroversion at the age of about 35 years old, died in their forties, indicating early-onset Alzheimer disease. ③The sequencing results showed that, in exon 5 of PSEN1of the proband, a reported heterozygous mutation (c.346G>A, p. Glu116Lys) was identified. The same heterozygous mutation was found respectively in his son, a son (Ⅲ_11,45 years old) and a grandson (Ⅳ_11,7 years old) of a paternal aunt, and a daughter (Ⅲ_15,29 years old) of another paternal aunt. The son of the paternal aunt who had the same mutation with the proband was 45 years old without any symptoms.

Clinical and molecular genetic features of the proband′s pedigree were clearly definite. The results confirmed the diagnosis of early-onset Alzheimer disease. It will be helpful for the genetic counseling and the prenatal diagnosis of the next generation of the family.