Adult-onset autosomal dominant leukodystrophy and neuronal intranuclear inclusion disease: lessons from two new Chinese families

Chen, Shuai; Zou, Jin-Long; He, Shuang; Li, Wei; Zhang, Jiewen; Li, Shu-Jian

doi:10.1007/s10072-022-06057-0

Cited by 4 publications

(3 citation statements)

References 24 publications

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“…We did not explore the effects of other forms of dysautonomia or conditions commonly related to cardiovascular dysautonomia, such as REM Sleep Behavior Disorder. Finally, we exclusively focused on NOH associations with PD-related SNPs, leaving out other potentially related genes such as LMNB1, CHRNA3, GBE1, and DBH [ 44 , 45 , 46 , 47 ]. Work for the future will be to use the identified markers to examine the 304 subjects longitudinally to detect if gene markers portend a high risk of NOH development over time or in response to dopaminergic treatment when introduced.…”

Section: Discussionmentioning

confidence: 99%

Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study

et al. 2023

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The genetic basis of Neurogenic Orthostatic Hypotension (NOH) in Parkinson’s disease (PD) has been inadequately explored. In a cross-sectional study, we examined the association between NOH and PD-related single-nucleotide polymorphisms (SNPs) and mapped their effects on gene expression and metabolic and signaling pathways. Patients with PD, free from pathological conditions associated with OH, and not taking OH-associated medications were included. NOH was defined as per international guidelines. Logistic regression was used to relate SNPs to NOH. Linkage-disequilibrium analysis, expression quantitative trait loci, and enrichment analysis were used to assess the effects on gene expression and metabolic/signaling pathways. We included 304 PD patients in the study, 35 of whom had NOH (11.5%). NOH was more frequent in patients with SNPs in SNCA, TMEM175, FAM47E-STBD1, CCDC62, SCN3A, MIR4696, SH3GL2, and LZTS3/DDRGK1 and less frequent in those with SNPs in ITGA8, IP6K2, SIPA1L2, NDUFAF2. These SNPs affected gene expression associated with the significant hierarchical central structures of the autonomic nervous system. They influenced several metabolic/signaling pathways, most notably IP3/Ca++ signaling, the PKA-CREB pathway, and the metabolism of fatty acids. These findings provide new insights into the pathophysiology of NOH in PD and may provide targets for future therapies.

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Section: Discussionmentioning

confidence: 99%

Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study

et al. 2023

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“…However, the asymmetrical involvement of the brain would not be typical for a leukodystrophy, although the field of genetically defined mitochondrial leukodystrophies continues to expand [ 35 ]. Moreover, for some recently described genetically defined leukodystrophies with adult onset, neuropathological correlation was not available or has not been reported [ 4 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

A case of primary optic pathway demyelination caused by oncocytic oligodendrogliopathy of unknown origin

Hametner

Silvaieh

Thurnher

et al. 2022

acta neuropathol commun

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We report the case of a 22-year-old woman presenting with an acute onset of dizziness, gait dysbalance and blurred vision. Magnetic resonance imaging included 3 Tesla and 7 Tesla imaging and revealed a T2-hyperintense, T1-hypointense, non-contrast-enhancing lesion strictly confined to the white matter affecting the right optic radiation. An extensive ophthalmologic examination yielded mild quadrantanopia but no signs of optic neuropathy. The lesion was biopsied. The neuropathological evaluation revealed a demyelinating lesion with marked tissue vacuolization and granular myelin disintegration accompanied by mild T cell infiltration and a notable absence of myelin uptake by macrophages. Oligodendrocytes were strikingly enlarged, displaying oncocytic characteristics and showed cytoplasmic accumulation of mitochondria, which had mildly abnormal morphology on electron microscopy. The diagnosis of multiple sclerosis was excluded. Harding's disease, a variant of Leber's hereditary optic neuropathy, was then suspected. However, neither PCR for relevant mutations nor whole exome sequencing yielded known pathogenetic mutations in the patient's genome. We present a pattern of demyelinating tissue injury of unknown etiology with an oncocytic change of oligodendrocytes and a lack of adequate phagocytic response by macrophages, which to the best of our knowledge, has not been described before.

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“…High‐throughput sequencing was carried out by Illumina NovaSeq 6000 series sequencer (PE150). Genetic variants were filtered and annotated as previously described (Chen et al, 2022 ). The average sequencing depth was 229×, and the coverage rate was 99.81%.…”

Section: Clinical Reportmentioning

confidence: 99%

Complex cerebrovascular diseases in Roberts syndrome caused by novel biallelic ESCO2 variations

Chen

et al. 2023

Molec Gen & Gen Med

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Objective Roberts syndrome (RBS), also known as Roberts‐SC phocomelia syndrome, is a rare autosomal recessive developmental disorder caused by mutations in the ESCO2 gene. Cardinal clinical manifestations are pre‐ and postnatal growth retardation and craniofacial and limb malformations. Here, we report RBS in a Chinese adolescent with novel biallelic ESCO2 variations and complex cerebrovascular diseases. Methods Medical history, neurological examinations, neuroimaging, and pathology were collected in the proband and the family. Whole exome sequencing (WES) with copy number variation analysis was performed to screen for genetic variations. Results The clinical features of the proband were craniofacial and limb malformations together with complex cerebrovascular diseases. She suffered ischemic stroke at 6 years old and died of cerebellar hemorrhage secondary to an aneurysm at 13 years old. Besides, neuroimaging showed the triad of leukoencephalopathy, calcifications, and cysts. Brain histopathology revealed angiomatous changes and perivascular cysts suggesting chronic small cerebral vasculopathy. Whole exome sequencing (WES) identified novel biallelic variations in the ESCO2 gene (c.1220A>T, p.H407L and c.1562delC, p.A521fs). Conclusions We describe complex cerebrovascular diseases in Roberts syndrome caused by novel ESCO2 biallelic variations. This case expands not only the cerebral involvement in Roberts syndrome but also the disease spectrum of the neuroimaging triad with leukoencephalopathy, calcifications, and cysts.

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Adult-onset autosomal dominant leukodystrophy and neuronal intranuclear inclusion disease: lessons from two new Chinese families

Cited by 4 publications

References 24 publications

Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study

Genetics of Neurogenic Orthostatic Hypotension in Parkinson’s Disease, Results from a Cross-Sectional In Silico Study

A case of primary optic pathway demyelination caused by oncocytic oligodendrogliopathy of unknown origin

Complex cerebrovascular diseases in Roberts syndrome caused by novel biallelic ESCO2 variations

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