Variant late‐infantile neuronal ceroid lipofuscinosis due to a novel heterozygous <i>CLN8</i> mutation and <i>de novo</i> 8p23.3 deletion

Allen, NM; O'hIci, Bronagh; Anderson, Glenn; Nestor, Therese; Lynch, Sally Ann; T, King

doi:10.1111/j.1399-0004.2011.01777.x

Cited by 19 publications

(21 citation statements)

References 4 publications

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“…Missense variants and haploinsufficiency have been previously reported but with a more severe phenotype than our patients 5 , 6 , 12 , 15 , 16 . It is possible that the novel missense variant, c.200C > T (p.A67V) in the CLN8 gene in our family results in a milder disease.…”

Section: Discussionsupporting

confidence: 46%

“…The variant late infantile form of NCL is common in Turkish and Italian populations 9 , 10 , 11 , 12 presenting around 3–7 years of age with motor decline, severe epilepsy and severe vision loss 6 , 9 , 10 . We compare the variation in the clinical presentation of our patients with other previously reported individuals with CLN8 in the Supplementary table 6 , 7 , 11 , 12 , 13 , 14 , 15 . Other common findings reported include dystonia, ataxia and other pyramidal signs.…”

Section: Discussionmentioning

confidence: 99%

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Atypical presentation of neuronal ceroid lipofuscinosis type 8 in a sibling pair and review of the eye findings and neurological features

Sánchez

Yan

Richards

et al. 2016

American Journal of Ophthalmology Case Reports

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PurposeTo report atypical presentation of neuronal ceroid lipofuscinoses type 8 (CLN8) to the eye clinic and review clinical features of CLN8.ObservationsDetailed eye exam by slit lamp exam, indirect ophthalmoscopy, fundus photography, optical coherence tomography, visual fields and electroretinogram (ERG). Molecular genetic testing using Next Generation Sequencing panel (NGS) and array Comparative Genomic Hybridization (aCGH).The siblings in this study presented to the eye clinic with retinitis pigmentosa and cystoid macular edema, and a history of seizures but no severe neurocognitive deficits or regression. Genetic testing identified a c.200C > T (p.A67V) variant in the CLN8 gene and a deletion encompassing the entire gene. Electron microscopy of lymphocytes revealed fingerprint inclusions in both siblings.Conclusionsand Importance: Pathogenic variants in CLN8 account for the retinitis pigmentosa and seizures in our patients however, currently, they do not have regression or neurocognitive decline. The presentation of NCL can be very diverse and it is important for ophthalmologists to consider this in the differential diagnosis of retinal disorders with seizures or other neurological features. Molecular genetic testing of multiple genes causing isolated and syndromic eye disorders using NGS panels and aCGH along with additional complementary testing may often be required to arrive at a definitive diagnosis.

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Section: Discussionsupporting

confidence: 46%

Section: Discussionmentioning

confidence: 99%

Atypical presentation of neuronal ceroid lipofuscinosis type 8 in a sibling pair and review of the eye findings and neurological features

Sánchez

Yan

Richards

et al. 2016

American Journal of Ophthalmology Case Reports

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“…In contrast, the missense variant results in a milder and early-adult-onset form characterized by progressive myoclonic epilepsy alone without visual failure [ 20 ]. We reviewed the NCL Mutation Database ( http://www.ucl.ac.uk/ncl/ ) and the updated literature to analyze the phenotype-variant correlation for the NCL patients with CLN8 variants [ 17 , 21 – 24 ]. We found that the patients carrying CLN8 null variants presented earlier onset and more progressive disease course than the patients carrying CLN8 missense variants.…”

Section: Discussionmentioning

confidence: 99%

Identification of two novel null variants in CLN8 by targeted next-generation sequencing: first report of a Chinese patient with neuronal ceroid lipofuscinosis due to CLN8 variants

et al. 2018

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BackgroundNeuronal ceroid lipofuscinoses (NCLs) are one of the most frequent childhood-onset neurodegenerative pathologies characterized by seizures, progressive cognitive decline, motor impairment and loss of vision. For the past two decades, more than 430 variants in 13 candidate genes have been identified in the affected patients. Most of the variants were almost exclusively reported in Western patients, and very little clinical and genetic information was available for Chinese patients.Case presentationWe report a Chinese boy whose clinical phenotypes were suspected to be NCL, including intractable epilepsy, cognitive and motor decline and progressive vision loss. Using targeted next-generation sequencing, two novel null variants in CLN8 (c.298C > T, p.Gln100Ter; c.551G > A, p.Trp184Ter) were detected in this patient in trans model. These two variants were interpreted as pathogenic according to the variant guidelines of the American College of Medical Genetics and Genomics.ConclusionsThis is the first case report of NCL due to CLN8 variants in China. Our findings expand the variant diversity of CLN8 and demonstrate the tremendous diagnosis value of targeted next-generation sequencing for pediatric NCLs.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0535-7) contains supplementary material, which is available to authorized users.

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“…One Irish patient has already been reported with a de novo terminal deletion of the short arm of chromosome 8p23.3 (Allen et al. ). One Turkish family carries a 2.6 kb intragenic deletion in CLN8 that causes more severe disease than most other mutations (Reinhardt et al.…”

Section: Introductionmentioning

confidence: 99%

CLN8 disease caused by large genomic deletions

Beesley

Guerreiro

Brás

et al. 2016

Molec Gen & Gen Med

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BackgroundThe presence of deletions can complicate genetic diagnosis of autosomal recessive disease.MethodThe DNA of patients was analyzed in a diagnostic setting.ResultsWe present three unrelated patients each carrying deletions that encompass the 37 kb CLN8 gene and discuss their phenotype. Two of the cases were hemizygous for a mutant allele – their deletions unmasked a mutation in CLN8 on the other chromosome.ConclusionMicroarray analysis is recommended in any patient suspected of NCL who is apparently homozygous for a mutation that is not present in one of the parents or when the family has no known consanguinity.

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Variant late‐infantile neuronal ceroid lipofuscinosis due to a novel heterozygous CLN8 mutation and de novo 8p23.3 deletion

Cited by 19 publications

References 4 publications

Atypical presentation of neuronal ceroid lipofuscinosis type 8 in a sibling pair and review of the eye findings and neurological features

Atypical presentation of neuronal ceroid lipofuscinosis type 8 in a sibling pair and review of the eye findings and neurological features

Identification of two novel null variants in CLN8 by targeted next-generation sequencing: first report of a Chinese patient with neuronal ceroid lipofuscinosis due to CLN8 variants

CLN8 disease caused by large genomic deletions

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