Yun Joong Kim1, Chul Hyoung Lyoo2, Sangkyoon Hong3, Nan Young Kim3, Myung Sik Lee4. 1. ILSONG Institute of Life Science, Hallym University, Anyang, Republic of Korea; Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea; Hallym Institute of Translational Genomics and Bioinformatics, Anyang, Republic of Korea. Electronic address: yunkim@hallym.ac.kr. 2. Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 3. Hallym Institute of Translational Genomics and Bioinformatics, Anyang, Republic of Korea. 4. Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: mslee@yuhs.ac.
Abstract
BACKGROUND: PLA2G6-associated neurodegeneration (PLAN) encompasses infantile- or atypical neuroaxonal dystrophy, and adult-onset dystonia-parkinsonism. Examination of the intrafamilial phenotypic variability of PLAN by neuroimaging data and background genetic differences has not been reported. METHODS: We report clinical, genetic (whole exome sequencing data), and neuroimaging findings from a Korean PLAN family showing intrafamilial phenotypic variability. Non-synonymous single nucleotide variants (SNVs) in Mendelian disorder genes related to parkinsonism, dystonia, ataxia, dementia or neurodegeneration with brain iron accumulation were compared between affected siblings. RESULTS: The proband presented with adult-onset dystonia-parkinsonism, whereas the affected brother presented with childhood-onset atypical neuroaxonal dystrophy. In the proband, an [18F]FP-CIT PET study showed markedly reduced uptake in the whole putamen, but fluid attenuated inversion recovery and gradient echo MRI studies revealed mild hypointensities in the substantia nigra and the putamen and severe hypointensities in the pallidum. On the other hand, in the affected brother, MRI scans showed severe hypointensities in the substantia nigra and the pallidum, and a [18F]-FP-CIT PET scan was normal. Analysis of the non-synonymous SNVs that were not shared between the two family members revealed non-synonymous SNVs related to parkinsonism including a novel heterozygous mutation (p.T44N) in FBX07 (PARK15) only in the proband, and non-synonymous SNVs related to neurodegeneration with brain iron accumulation in the affected brother. CONCLUSION: Our data suggests that dopaminergic neuronal degeneration may not secondary to iron accumulation in PLAN. The burden of pathogenic SNVs may influence the intrafamilial phenotypic variability of PLAN.
BACKGROUND:PLA2G6-associated neurodegeneration (PLAN) encompasses infantile- or atypical neuroaxonal dystrophy, and adult-onset dystonia-parkinsonism. Examination of the intrafamilial phenotypic variability of PLAN by neuroimaging data and background genetic differences has not been reported. METHODS: We report clinical, genetic (whole exome sequencing data), and neuroimaging findings from a Korean PLAN family showing intrafamilial phenotypic variability. Non-synonymous single nucleotide variants (SNVs) in Mendelian disorder genes related to parkinsonism, dystonia, ataxia, dementia or neurodegeneration with brain iron accumulation were compared between affected siblings. RESULTS: The proband presented with adult-onset dystonia-parkinsonism, whereas the affected brother presented with childhood-onset atypical neuroaxonal dystrophy. In the proband, an [18F]FP-CIT PET study showed markedly reduced uptake in the whole putamen, but fluid attenuated inversion recovery and gradient echo MRI studies revealed mild hypointensities in the substantia nigra and the putamen and severe hypointensities in the pallidum. On the other hand, in the affected brother, MRI scans showed severe hypointensities in the substantia nigra and the pallidum, and a [18F]-FP-CIT PET scan was normal. Analysis of the non-synonymous SNVs that were not shared between the two family members revealed non-synonymous SNVs related to parkinsonism including a novel heterozygous mutation (p.T44N) in FBX07 (PARK15) only in the proband, and non-synonymous SNVs related to neurodegeneration with brain iron accumulation in the affected brother. CONCLUSION: Our data suggests that dopaminergic neuronal degeneration may not secondary to iron accumulation in PLAN. The burden of pathogenic SNVs may influence the intrafamilial phenotypic variability of PLAN.
Authors: Yalan Wan; Yanyan Jiang; Zhiying Xie; Chen Ling; Kang Du; Ran Li; Yun Yuan; Zhaoxia Wang; Wei Sun; Haiqiang Jin Journal: Front Neurol Date: 2022-07-13 Impact factor: 4.086
Authors: Jae-Hyeok Lee; Jongkyu Park; Ho-Sung Ryu; Hyeyoung Park; Young Eun Kim; Jin Yong Hong; Sang Ook Nam; Young-Hee Sung; Seung-Hwan Lee; Jee-Young Lee; Myung Jun Lee; Tae-Hyoung Kim; Chul Hyoung Lyoo; Sun Ju Chung; Seong Beom Koh; Phil Hyu Lee; Jin Whan Cho; Mee Young Park; Yun Joong Kim; Young H Sohn; Beom Seok Jeon; Myung Sik Lee Journal: J Mov Disord Date: 2016-01-25