Goldman Jill S, Miller Bruce L, Safar Jiri, de Tourreil Sunita, Martindale Jennifer L, Prusiner Stanley B, Geschwind Michael D
University of California, Memory and Aging Center, San Francisco 94143-1207, USA.
Arch Neurol. 2004 Feb;61(2):213-6. doi: 10.1001/archneur.61.2.213.
Approximately 2% of Alzheimer disease cases and 10% to 15% of prion disease cases are due to mutations in autosomal dominant genes. Mutations have been found in patients without family histories of neurological disease.
To emphasize the need for consideration of a genetic etiology of prion disease and early-onset Alzheimer disease, regardless of the absence of a significant family history, as well as the need for pretest genetic counseling of all patients or their families.
Three case reports.
Patient 1, a 53-year-old man with possible Creutzfeldt-Jakob disease, was enrolled in a research study that included sequencing of the prion protein gene. Although there was no family history of neurological disease, an E200K mutation was found. This unexpected result caused the family significant distress. Patient 2, a 55-year-old woman with biopsy-proven Creutzfeldt-Jakob disease, participated in a prion disease research study. Her family was counseled about the possibility of hereditary Creutzfeldt-Jakob disease, despite the lack of family history. After assessing the ramifications, the family decided not to learn about the patient's genetic test results. Patient 3 was a 54-year-old man with a 6-year history of memory loss. A diagnosis of probable Alzheimer disease was given, and the patient and his family were counseled on the availability of presenilin 1 testing, although there was no known family history of dementia. The family agreed to testing, and a presenilin 1 mutation was identified.
Certain neurodegenerative diseases may have a genetic etiology, despite the lack of a positive family history. Revealing a newly discovered hereditary cause of Creutzfeldt-Jakob disease or Alzheimer disease can have a profound effect on families. Pretest counseling on genetic issues is essential to better prepare families and to allow them to make an informed choice about learning genetic test results.
约2%的阿尔茨海默病病例以及10%至15%的朊病毒病病例是由常染色体显性基因突变所致。在无神经疾病家族史的患者中也发现了此类突变。
强调无论有无明显家族病史，都需考虑朊病毒病和早发性阿尔茨海默病的遗传病因，以及对所有患者或其家属进行检测前遗传咨询的必要性。
三例病例报告。
患者1为一名53岁男性，可能患有克雅氏病，参与了一项包括朊蛋白基因测序的研究。尽管其无神经疾病家族史，但发现了E200K突变。这一意外结果给其家族带来了极大痛苦。患者2为一名55岁女性，经活检确诊为克雅氏病，参与了一项朊病毒病研究。尽管其家族无相关病史，但已就遗传性克雅氏病的可能性对其家属进行了咨询。在评估后果后，其家属决定不了解患者的基因检测结果。患者3为一名54岁男性，有6年记忆丧失病史。诊断为可能的阿尔茨海默病，尽管其家族无痴呆症病史，但已就早老素1检测事宜对患者及其家属进行了咨询。其家属同意检测，结果发现了早老素1突变。
某些神经退行性疾病可能存在遗传病因，尽管无阳性家族病史。揭示新发现的克雅氏病或阿尔茨海默病的遗传病因可能会对家族产生深远影响。检测前的遗传问题咨询对于让家族做好更好的准备并使其能够就是否了解基因检测结果做出明智选择至关重要。
