Isaacs David, Claassen Daniel, Bowman Aaron B, Hedera Peter
Department of Neurology, Vanderbilt University Medical Center, 1301 Medical Center Dr. Suite 3930, Nashville, TN 37232-5400, USA.
Department of Pediatrics, Pediatric Neurology, Vanderbilt University Medical Center, Nashville, TN 37232-2594, USA.
Brain Sci. 2017 Jun 24;7(7):71. doi: 10.3390/brainsci7070071.
mutations are the most common cause of early-onset Parkinson's disease. No genotype-phenotype correlation exists, and phenotypic variability is quite common. We report two siblings with confirmed identical compound heterozygous mutations in the gene manifesting strikingly different phenotypes. The older brother demonstrated marked parkinsonism by his mid-20's, whereas the younger brother developed exercise-induced dystonia in his mid-30's with no subsequent clinical progression, highlighting the clinical heterogeneity of the disease and implying the role of other genetic and/or environmental factors in disease progression. The younger sibling, despite his mild symptoms, had a clearly abnormal dopamine transporter (DaT)-SPECT scan. To our knowledge, this is the first such reported case of an abnormal DaT-SPECT scan in a patient with biallelic mutations who does not meet the clinical criteria for Parkinson's disease.
突变是早发性帕金森病最常见的病因。不存在基因型与表型的相关性，表型变异性相当常见。我们报告了两名兄弟姐妹，他们在该基因中具有经确认相同的复合杂合突变，但表现出截然不同的表型。哥哥在25岁左右出现明显的帕金森综合征，而弟弟在35岁左右出现运动诱发性肌张力障碍，且后续无临床进展，这突出了该疾病的临床异质性，并暗示了其他遗传和/或环境因素在疾病进展中的作用。弟弟尽管症状较轻，但多巴胺转运体（DaT）单光子发射计算机断层扫描（SPECT）结果明显异常。据我们所知，这是首例报道的双等位基因突变患者中DaT-SPECT扫描异常但不符合帕金森病临床标准的病例。
