Lipofuscinosis neuronal ceroidea: algoritmo diagnóstico y descripción clínica de las variantes infantil tardía finlandesa (CLN5) y turca (CLN7)

Pérez-Poyato, María S.; Milà-Recasens, M; Ferrer-Abizanda, I; Cusí-Sánchez,; Vázquez-López, M; Camino-León, R; Mj, Coll-Rosell; Gort, Laura; Pineda-Marfà, M

doi:10.33588/rn.5409.2011657

Cited by 3 publications

(6 citation statements)

References 21 publications

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“…Following the original description of eight Finnish patients affected with CLN5 disease, 6 a total of 19 cases with late infantile onset have so far been described. 7,8,[14][15][16][17][18][19] The clinical presentation in reported non-Finnish cases seems relatively uniform regardless of their genetics, with close similarities to our cohort. The age at onset ranged from preschool to school age (2y 6mo-9y; median age 4y 7mo), in accordance with the results our study (2-7y 7mo; median age 5y).…”

Section: Discussionsupporting

confidence: 77%

“…Following the original description of eight Finnish patients affected with CLN5 disease, a total of 19 cases with late infantile onset have so far been described . The clinical presentation in reported non‐Finnish cases seems relatively uniform regardless of their genetics, with close similarities to our cohort.…”

Section: Discussionmentioning

confidence: 70%

“…Likewise, there is a concordance in the early occurrence of language impairment, which was recorded in about 50% of patients at onset, or which developed within 1 to 2 years. [15][16][17][18][19] A further similarity relates to the age at onset of visual impairment: it occurred relatively late (median age 8y in all studies) as it is commonly observed in all variant late infantile NCL forms. Similarly, seizures were not early manifestations of the disease (median ages of onset 6y 6mo and 8y respectively), and progression of epilepsy was always slower than in infantile and late infantile NCL.…”

Section: Discussionmentioning

confidence: 78%

“…The age at onset ranged from preschool to school age (2y 6mo–9y; median age 4y 7mo), in accordance with the results our study (2–7y 7mo; median age 5y). Likewise, there is a concordance in the early occurrence of language impairment, which was recorded in about 50% of patients at onset, or which developed within 1 to 2 years . A further similarity relates to the age at onset of visual impairment: it occurred relatively late (median age 8y in all studies) as it is commonly observed in all variant late infantile NCL forms.…”

Section: Discussionmentioning

confidence: 99%

“…At onset, similar scores were observed in all patients regardless of the mutation(s) they harboured (mean 22.3 [1.0]; score range 20-23). A modest rating decrease was observed during the next 3 years and was relatively homogenous among all children (mean 19.6 [2.2]; score range [15][16][17][18][19][20][21][22][23]. Thereafter, differences between the patients were observed.…”

Section: Clinical Course and Genotype-phenotype Relationshipmentioning

confidence: 99%

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Phenotype and natural history of variant late infantile ceroid‐lipofuscinosis 5

Simonati

Williams

Nardocci³

et al. 2017

Develop Med Child Neuro

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Clinical Course and Genotype-phenotype Relationshipmentioning

confidence: 99%

See 3 more Smart Citations

Phenotype and natural history of variant late infantile ceroid‐lipofuscinosis 5

Simonati

Williams

Nardocci³

et al. 2017

Develop Med Child Neuro

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A novel pathogenic frameshift variant unmasked by a large de novo deletion at 13q21.33-q31.1 in a Chinese patient with neuronal ceroid lipofuscinosis type 5

Fan

Zhang

et al. 2020

BMC Med Genet

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Background Neuronal ceroid lipofuscinosis type 5 (CLN5) is a rare form of neuronal ceroid lipofuscinoses (NCLs) which are a group of inherited neurodegenerative diseases characterized by progressive intellectual and motor deterioration, visual failure, seizures, behavioral changes and premature death. CLN5 was initially named Finnish variant late infantile NCL, it is now known to be present in other ethnic populations and with variable age of onset. Few CLN5 patients had been reported in Chinese population. Case presentation In this paper, we report the symptoms of a Chinese patient who suffer from developmental regression and grand mal epilepsy for several years. The DNA was extracted from peripheral blood of proband and both parents, and then whole exome sequencing was performed using genomic DNA. Both sequence variants and copy number variants (CNVs) were analyzed and classified according to guidelines. As the result, a novel frameshift mutation c.718_719delAT/p.Met240fs in CLN5 and a de novo large deletion at 13q21.33-q31.1 which unmasked the frameshift mutation were identified in the proband. Despite the large de novo deletion, which can be classified as a pathogenic copy number variant (CNV), the patient’s clinical presentation is mostly consistent with that of CLN5, except for early developmental delay which is believed due to the large deletion. Both variants were detected simultaneously by exome sequencing. Conclusions This is the first report of whole gene deletion in combination with a novel pathogenic sequence variant in a CLN5 patient. The two mutations detected with whole exome sequencing simultaneously proved the advantage of the sequencing technology for genetic diagnostics.

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Next-Generation Sequencing Analysis Reveals Novel Pathogenic Variants in Four Chinese Siblings With Late-Infantile Neuronal Ceroid Lipofuscinosis

et al. 2019

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Neuronal Ceroid Lipofuscinoses (NCLs) are progressive degenerative diseases mainly affect brain and retina. They are characterized by accumulation of autofluorescent storage material, mitochondrial ATPase subunit C, or sphingolipid activator proteins A and D in lysosomes of most cells. Heterogenous storage material in NCLs is not completely disease-specific. Most of CLN proteins and their natural substrates are not well-characterized. Studies have suggested variants of Late-Infantile NCLs (LINCLs) include the major type CLN2 and minor types CLN5, CLN6, CLN7, and CLN8. Therefore, combination of clinical and molecular analysis has become a more effective diagnosis method. We studied 4 late-infantile NCL siblings characterized by seizures, ataxia as early symptoms, followed by progressive regression in intelligence and behavior, but mutations are located in different genes. Symptoms and progression of 4 types of LINCLs are compared. Pathology of LINCLs is also discussed. We performed Nest-Generation Sequencing on these phenotypically similar families. Three novel variants c.1551+1insTGAT in TPP1, c.244G>T in CLN6, c.554-5A>G in MFSD8 were identified. Potential outcome of the mutations in structure and function of proteins are studied. In addition, we observed some common and unique clinical features of Chinese LINCL patient as compared with those of Western patients, which greatly improved our understanding of the LINCLs.

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Lipofuscinosis neuronal ceroidea: algoritmo diagnóstico y descripción clínica de las variantes infantil tardía finlandesa (CLN5) y turca (CLN7)

Cited by 3 publications

References 21 publications

Phenotype and natural history of variant late infantile ceroid‐lipofuscinosis 5

Phenotype and natural history of variant late infantile ceroid‐lipofuscinosis 5

A novel pathogenic frameshift variant unmasked by a large de novo deletion at 13q21.33-q31.1 in a Chinese patient with neuronal ceroid lipofuscinosis type 5

Next-Generation Sequencing Analysis Reveals Novel Pathogenic Variants in Four Chinese Siblings With Late-Infantile Neuronal Ceroid Lipofuscinosis

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