Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Flemington Road, Parkville, Victoria, 3052, Australia; Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria, 3052, Australia.
Department of Neurology, Rabin Medical Center, Campus Beilinson, Petach Tiqva, Israel; Sacler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Parkinsonism Relat Disord. 2019 Jul;64:308-311. doi: 10.1016/j.parkreldis.2019.03.013. Epub 2019 Mar 22.
Bi-allelic mutations in PARK7 are a rare cause of autosomal recessive early onset Parkinson's disease (EO-PD). To date, 30 individuals harbouring 20 unique causative variants have been described. Understanding of the spectrum of clinical features and natural history of PARK7 mediated EO-PD remain limited.
We studied a family with three offspring, two of whom were affected with EO-PD. Family members underwent detailed clinical examination and DNA samples from both affected individuals and parents were analysed by exome sequencing.
Two brothers of Iranian descent presented at age 29 years with Parkinsonism associated with high-pitched voice and hypomimia. The brothers were followed over a six and fifteen-year period and displayed typical levodopa responsive slowly-progressive Parkinsonism. A novel homozygous frameshift mutation in PARK7 [NM_007262.4:c.90dupG, p(Ile31Aspfs*2)] was identified.
Here we report the clinical presentation and progression of EO-PD in brothers with a novel pathogenic PARK7 variant. We expand the clinical phenotype and provide an update of clinical and pathological features of the disorder.
PARK7 的双等位基因突变是常染色体隐性早发性帕金森病（EO-PD）的罕见原因。迄今为止，已有 30 名个体携带 20 种独特的致病变异体被描述。对 PARK7 介导的 EO-PD 的临床特征和自然病史的了解仍然有限。
我们研究了一个有三个后代的家庭，其中两个患有 EO-PD。对家庭成员进行了详细的临床检查，并通过外显子组测序分析了两名受影响个体和父母的 DNA 样本。
两名伊朗裔兄弟在 29 岁时出现帕金森病，伴有高音调声音和表情减少。这对兄弟被随访了六年和十五年，表现出典型的左旋多巴反应性缓慢进展性帕金森病。发现 PARK7 中的一个新的纯合移码突变 [NM_007262.4：c.90dupG，p（Ile31Aspfs*2）]。
在这里，我们报告了一对兄弟携带新的致病性 PARK7 变异体的 EO-PD 的临床表现和进展。我们扩展了临床表型，并提供了该疾病的临床和病理特征的最新信息。
