Department of Neurology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
J Hum Genet. 2019 Jan;64(1):55-59. doi: 10.1038/s10038-018-0519-7. Epub 2018 Oct 9.
PLA2G6-associated neurodegeneration (PLAN) comprises heterogeneous neurodegenerative disorders, including infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation 2B, and Parkinson disease 14 (PARK14). In addition, very recently, PLA2G6 mutations have been reported to represent a phenotype of hereditary spastic paraplegia (HSP). In this study, we screened 383 HSP families to clarify the frequency of PLA2G6 mutations in the Japan Spastic Paraplegia Research Consortium, and revealed the clinical characteristics of HSP with PLA2G6 mutations. We found three families with compound heterozygous mutations of the PLA2G6 gene, c.517 C > T/c.1634A > G, c.662 T > C/c.991 G > T, and c.1187-2 A > G/c.1933C > T, and one family with a homozygous mutation of the PLA2G6 gene, c.1904G > A/c.1904G > A. All three families with compound heterozygous mutations presented a uniform phenotype of a complicated form of HSP with infantile/child-onset spastic paraplegia, cerebellar ataxia, and mental retardation. On the other hand, the family with a homozygous mutation presented a late-onset complicated form of HSP with parkinsonism. This study may extend the clinical and genetic findings for PLAN.
PLA2G6 相关神经退行性疾病（PLAN）包括多种神经退行性疾病，包括婴儿型神经轴索性营养不良、脑铁蓄积 2B 型神经退行性疾病和帕金森病 14 型（PARK14）。此外，最近 PLA2G6 突变被报道代表遗传性痉挛性截瘫（HSP）的表型。在这项研究中，我们对 383 个 HSP 家系进行了筛查，以阐明日本痉挛性截瘫研究联合会中 PLA2G6 突变的频率，并揭示了具有 PLA2G6 突变的 HSP 的临床特征。我们发现了三个具有 PLA2G6 基因突变的复合杂合子的家系，c.517C>T/c.1634A>G、c.662T>C/c.991G>T 和 c.1187-2A>G/c.1933C>T，以及一个具有 PLA2G6 基因突变的纯合子的家系，c.1904G>A/c.1904G>A。所有三个具有复合杂合突变的家系均表现出一种复杂形式 HSP 的一致表型，伴有婴儿/儿童起病的痉挛性截瘫、小脑共济失调和智力障碍。另一方面，具有纯合突变的家系表现为迟发性复杂形式的 HSP 伴帕金森病。本研究可能扩展了 PLAN 的临床和遗传发现。
