Blood−brain barrier permeability in a patient with Labrune syndrome due to <scp>SNORD</scp>118 mutations: would this be the mechanism for progressive worsening?

Pessoa, André Luiz Santos

doi:10.1111/ene.13671

Cited by 6 publications

(5 citation statements)

References 8 publications

(10 reference statements)

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“…Watson-Crick base-pairing between the 5 0 end and 3 0 extension of human pre-U8 (Badrock et al, 2020). Indeed, 54 of 64 patients in our cohort were heterozygous for a mutation involving one of these seven nucleotides, an enrichment seen in other molecularly-proven cases of LCC published to date (eight of 17 patients with recorded biallelic mutations) (Hermens, van der Knaap, Kamsteeg, & Willemsen, 2018;Iwama et al, 2017;Iwasaki et al, 2017;Jin et al, 2018;Osman et al, 2020;Pessoa, 2018;Taglia et al, 2018) (Table S2). Recognition that these 5 0 end and 3 0 extension variants represent hypomorphic alleles suggests the possibility to modify their expression, or their effect on pre-U8 processing, as a therapeutic strategy relevant to the majority of patients with LCC.…”

Section: Discussionmentioning

confidence: 70%

Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum

Crow

Marshall

Rice

et al. 2020

American J of Med Genetics Pt A

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Biallelic mutations in SNORD118, encoding the small nucleolar RNA U8, cause leukoencephalopathy with calcifications and cysts (LCC). Given the difficulty in interpreting the functional consequences of variants in nonprotein encoding genes, and the high allelic polymorphism across SNORD118 in controls, we set out to provide a description of the molecular pathology and clinical spectrum observed in a cohort of patients with LCC. We identified 64 affected individuals from 56 families. Age at presentation varied from 3 weeks to 67 years, with disease onset after age 40 years in eight patients. Ten patients had died. We recorded 44 distinct, likely pathogenic, variants in SNORD118. Fifty two of 56 probands were compound heterozygotes, with parental consanguinity reported in only three families. Forty nine of 56 probands were either heterozygous (46) or homozygous (three) for a mutation involving one of seven nucleotides that facilitate a novel intramolecular interaction between the 5′ end and 3′ extension of precursor‐U8. There was no obvious genotype–phenotype correlation to explain the marked variability in age at onset. Complementing recently published functional analyses in a zebrafish model, these data suggest that LCC most often occurs due to combinatorial severe and milder mutations, with the latter mostly affecting 3′ end processing of precursor‐U8.

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Section: Discussionmentioning

confidence: 70%

Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum

Crow

Marshall

Rice

et al. 2020

American J of Med Genetics Pt A

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“…With sparing of U fibers, corpus callosum, and gray matter, asymmetrical or relatively symmetrical leukoencephalopathy is usually distributed in periventricular and deep white matter, but relatively rare in the subcortical white matter. Multiple cysts can be observed over the entire brain parenchyma, especially appearing in a high frequency of the supratentorial region (2,17). Susceptibility-weighted imaging of patients often exhibits microbleedings and micro-calcifications, which implies that LCC might be associated with the abnormalities of micro-vessels.…”

Section: Discussionmentioning

confidence: 99%

“…Histopathological staining of biopsies from LCC patients can also be used for diagnosis. Angiomatous-like rearrangement of micro-vessels can always be identified as the primary prominent pathological feature, together with perivascular foci of dystrophic calcifications and hemosiderin deposits, hyaline degeneration, gliosis, and formation of Rosenthal fibers (1,2,8,9). However, LCC was easy to be misdiagnosed as cerebroretinal microangiopathy with calcifications and cysts, which is also called Coats plus syndrome and appears similar neuroimaging displays and histopathological features, caused by variants of the CTC1 gene (18).…”

Section: Discussionmentioning

confidence: 99%

“…Currently, symptomatic treatment is the primary therapy of LCC. Anti-epileptic therapy, corticosteroid therapy, and surgical techniques such as cystic puncture, cystic resection, and cystoventriculoperitoneal shunt may temporarily relieve the symptoms (2,3,6). Fay et al (24) reported an LCC case who got a marked clinical improvement by biweekly infusions of bevacizumab, an inhibitor of vascular endothelial growth factor, for more than 1 year.…”

Section: Discussionmentioning

confidence: 99%

“…Leukoencephalopathy with cerebral calcifications and cysts (LCC), first reported by Labrune in 1996, is a rare neurological microangiopathy characterized by leukoencephalopathy, intracranial calcifications, and cysts identified in cerebral imaging (1). About 100 cases have been reported so far (2)(3)(4)(5)(6). Leukoencephalopathy with cerebral calcifications and cysts has various clinical presentations, including seizures, cognitive decline, pyramidal/extrapyramidal signs, ataxia, and symptoms and signs consequent to increased intracranial pressure with the expanding cystic lesions (1,(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

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Case Report: Clinical Features of Childhood Leukoencephalopathy With Cerebral Calcifications and Cysts Due to SNORD118 Variants

Hong

Ren

et al. 2021

Front. Neurol.

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Background: Leukoencephalopathy with cerebral calcifications and cysts (LCC) is a rare autosomal recessive cerebral microangiopathy. Recently, biallelic variants in a non-protein-coding gene SNORD118 have been discovered to cause LCC.Case Presentation: We here report a genetically confirmed childhood case of LCC. The patient was a 4-year-and-1-month-old boy with focal seizures. The age at onset of his seizure was 10 days after birth. The seizures were well-controlled by antiepileptic treatment but reoccurred twice due to a head impact accident and a fever, respectively. He suffered from a self-limited esotropia and unsteady running gait during the seizure onset. He had the typical neuroimaging triad of multifocal intracranial calcifications, cysts, and leukoencephalopathy. Genetic analysis indicated that he carried compound heterozygous variants of n.*9C>T and n.3C>T in SNORD118, which were inherited from his parents.Conclusion: We report a childhood LCC case with compound heterozygous variants in SNORD118. To the best of our knowledge, the patient reported in our case had the youngest onset age of LCC with a determined genotype. The triad cerebral-imaging findings of calcifications, cysts, and leukoencephalopathy provide a crucial diagnostic basis. Moreover, the gene assessment, together with the clinical investigations, should be considered for the diagnosis of LCC.

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Surgical considerations in Labrune syndrome

Kobets¹,

Oriko

Groves³

et al. 2020

Childs Nerv Syst

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Blood−brain barrier permeability in a patient with Labrune syndrome due to SNORD118 mutations: would this be the mechanism for progressive worsening?

Cited by 6 publications

References 8 publications

Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum

Leukoencephalopathy with calcifications and cysts: Genetic and phenotypic spectrum

Case Report: Clinical Features of Childhood Leukoencephalopathy With Cerebral Calcifications and Cysts Due to SNORD118 Variants

Surgical considerations in Labrune syndrome

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