title: Identification of Novel Compound Mutations in PLA2G6-Associated Neurodegeneration Patient with Characteristic MRI Imaging.
abstract: Neurodegeneration with brain iron accumulation comprises a heterogeneous group of disorders characterized clinically by progressive motor dysfunction. Accurate identification of de novo and rare inherited mutations is important for determining causative genes of undiagnosed neurological diseases. In the present study, we report a unique case with cerebellar ataxia symptoms and social communication difficulties in an intermarriage family. MRI showed a marked cerebellar atrophy and the "eye-of-the-tiger"-like sign in the medial globus pallidus. Potential genetic defects were screened by whole-exome sequencing (WES) for the patient and four additional family members. A previously undescribed de novo missense mutation (c.1634A>G, p.K545R) in the exon 12 of the PLA2G6 gene was identified. A second rare variant c.1077G>A at the end of exon 7 was also identified, which was inherited from the mother, and resulted in a frame-shift mutation (c.1074_1077del.GTCG) due to an alternative splicing. In conclusion, the identification of the "eye-of-the-tiger"-like sign in the globus pallidus of the patient expands the phenotypic spectrum of PLA2G6-associated disorders and reveals its value in differential diagnosis of PLA2G6-associated disorders.
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Zhejiang, 325027, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Guo
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Zhejiang, 325027, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Zhejiang, 325027, China.
authors.forename: Huijie
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Radiology, The Second Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325027, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Zhejiang, 325027, China.
authors.forename: Jinchen
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Zhejiang, 325027, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Zhejiang, 325027, China.|Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100000, China.
authors.forename: Zhong Sheng
authors.initials: ZS
authors.lastname: Sun
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Zhejiang, 325027, China. chenxiangnj2005@aliyun.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Zhejiang, 325027, China. jdu@bcm.edu.|Anzhen Hospital, Capital Medical University, Beijing Collaborative Innovation Center for Cardiovascular Disorders in Ministry of Education, Anzhen Street, Chaoyang District, Beijing, 100029, China. jdu@bcm.edu.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Zhejiang, 325027, China. tcai@mail.nih.gov.|Experimental Medicine Section, NIDCR, NIH, Bethesda, MD, 20892, USA. tcai@mail.nih.gov.
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002648:Child; D005091:Exons / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D054522:Group VI Phospholipases A2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009410:Nerve Degeneration / Q000000981:diagnostic imaging* / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics; D000073359:Exome Sequencing
chemical_list: D022821:RNA Splice Sites; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human
keywords: Compound heterozygous mutations; Neurodegeneration with brain iron accumulation (NBIA); The eye-of-the-tiger sign; Whole-exome sequencing (WES); mirTrios