Alakbarzade Vafa, Iype Thomas, Chioza Barry A, Singh Royana, Harlalka Gaurav V, Hardy Holly, Sreekantan-Nair Ajith, Proukakis Christos, Peall Kathryn, Clark Lorraine N, Caswell Richard, Lango Allen Hana, Wakeling Matthew, Chilton John K, Baple Emma L, Louis Elan D, Warner Thomas T, Crosby Andrew H
Medical Research (Level 4) (V.A., B.A.C., G.V.H., H.H., A.S.-N., J.K.C., E.L.B., A.H.C.), University of Exeter Medical School, RILD Wellcome Wolfson Centre, Royal Devon & Exeter NHS Foundation Trust, United Kingdom; Reta Lila Weston Institute of Neurological Studies (V.A., T.T.W.), UCL Institute of Neurology, London, United Kingdom; Department of Neurology (T.I.), Government Medical College, Thiruvananthapuram, Kerala, India; Department of Anatomy and Microbiology (R.S.), Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India; Clinical Neuroscience (C.P.), Royal Free Campus, UCL Institute of Neurology, London, United Kingdom; Institute of Psychological Medicine and Clinical Neurosciences (K.P.), Cardiff University, Cardiff, United Kingdom; Taub Institute for Research on Alzheimer's Disease and the Aging Brain (L.N.C.), Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY; Institute of Biomedical and Clinical Science (R.C., H.L.A., M.W.), University of Exeter Medical School, United Kingdom; and Departments of Neurology and Chronic Disease Epidemiology and Center for Neuroepidemiology and Clinical Neurological Research (E.D.L.), Yale School of Medicine and Yale School of Public Health, Yale University, New Haven, CT.
Neurol Genet. 2019 Feb 4;5(1):e307. doi: 10.1212/NXG.0000000000000307. eCollection 2019 Feb.
To elucidate the genetic cause of a large 5 generation South Indian family with multiple individuals with predominantly an upper limb postural tremor and posturing in keeping with another form of tremor, namely, dystonic tremor.
Whole-genome single nucleotide polymorphism (SNP) microarray analysis was undertaken to look for copy number variants in the affected individuals.
Whole-genome SNP microarray studies identified a tandem duplicated genomic segment of chromosome 15q24 present in all affected family members. Whole-genome sequencing demonstrated that it comprised a ∼550-kb tandem duplication encompassing the entire gene.
The identification of a genomic duplication as the likely molecular cause of this condition, resulting in an additional gene copy in affected cases, adds further support for a causal role of this gene in tremor disorders and implicates increased expression levels of as a potential pathogenic mechanism.
阐明一个五代的南印度大家族的遗传病因，该家族中有多个个体主要表现为上肢姿势性震颤以及符合另一种震颤形式（即肌张力障碍性震颤）的姿势。
进行全基因组单核苷酸多态性（SNP）微阵列分析，以寻找患病个体中的拷贝数变异。
全基因组SNP微阵列研究在所有患病家庭成员中鉴定出15号染色体q24区域存在串联重复的基因组片段。全基因组测序表明，它包含一个约550kb的串联重复序列，涵盖整个 基因。
鉴定出基因组重复可能是这种疾病的分子病因，导致患病个体中额外存在一个 基因拷贝，这进一步支持了该基因在震颤疾病中的因果作用，并暗示 表达水平升高是一种潜在的致病机制。
