Juvenile neuronal ceroid-lipofuscinosis: clinical and molecular investigation in a large family in Brazil

Valadares, Eugênia Ribeiro; Pizarro, Mayara Xavier; Oliveira, Luiz Roberto de; Amorim, Regina Helena Caldas de; Pinheiro, Tarcísio Márcio Magalhães; Grieben, Ulrike; Santos, Helena Hollanda; Queiroz, Rachel Rabelo; Lopes, Guilherme de Castro; Godard, Ana Lúcia Brunialti

doi:10.1590/s0004-282x2011000100004

Cited by 9 publications

(4 citation statements)

References 15 publications

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“…However, Rett-like onset have been described for NCL7 disease, produced by MFSD8 gene mutations, and infantile NCL1 disease [ 9 , 15 , 16 ]. Similar autistic characteristics and stereotypic movements were observed in several forms of NCL [ 17 , 18 ].…”

Section: Introductionsupporting

confidence: 63%

A novel MFSD8 mutation in a Russian patient with neuronal ceroid lipofuscinosis type 7: a case report

Kozina

Окунева²,

Барышникова

et al. 2018

BMC Med Genet

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BackgroundNeuronal ceroid lipofuscinoses (NCLs) are the most common autosomal recessive neurodegenerative disorders in children. Clinical manifestations include progressive cognitive decline, motor impairment, ataxia, visual loss, seizures and early death. To date more than 440 NCL-causing mutations in 13 genes are known.Case presentationWe report clinical and genetic characteristics of a 5-year-old girl affected by ceroid lipofuscinosis type 7 (NCL7). She had progressive motor and mental deterioration since the age of 2,5 years. Later she developed progressive vision loss, stereotypies, action myoclonus and epilepsy. By the age of 5 years she stopped walking. Based on symptoms, diagnosis of Rett syndrome was suggested, but no abnormalities were detected in MeCP2. We identified a novel homozygous mutation in MFSD8 gene (c.525 T > A, p.Cys175Ter). To our knowledge, this is the first report of MFSD8 gene mutation in a Russian patient with variant late-infantile NCL.ConclusionsOur results enlarge mutational spectrum of ceroid lipofuscinosis type 7 and demonstrate tremendous diagnosis value of exome sequencing for pediatric NCLs. Also we confirmed that NCL should be suspected in patients with Rett-like phenotype at onset and negative MECP2 mutation.

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Section: Introductionsupporting

confidence: 63%

A novel MFSD8 mutation in a Russian patient with neuronal ceroid lipofuscinosis type 7: a case report

Kozina

Окунева²,

Барышникова

et al. 2018

BMC Med Genet

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“…The intronic changes found (n = 13) correspond to splicing regions, having been their pathogenicity confirmed for the most frequent variant in the TPP1/CLN2 gene, I7 c.887-10A>G, p.Pro295_Gly296insGluAsnPro (40) and the variant I13 c.1306+5G>A, p.Gly398_Leu435del in the ATP13A2/CLN12 gene (25). Five deletions have been described, spanning few nucleotides [e.g., E9 c.1107_1108delTG, p.Gly370Lysfs * 32 in the TPP1/CLN2 gene (Cordoba cohort)], large intragenic deletions (such as the most frequent variant of CLN3 disease, 1.02 kb deletion, c.462_677del) (36,41), or large chromosomal deletions (such as the deletion in the 8p23 region including the CLN8 gene) (28). The pathogenicity of the variants has only been defined in 37% of cases.…”

Section: The Genetic Background Of the Saandc Cohortmentioning

confidence: 99%

Neuronal ceroid lipofuscinosis in the South American-Caribbean region: An epidemiological overview

et al. 2022

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Neuronal ceroid lipofuscinoses (NCLs) comprise 13 hereditary neurodegenerative pathologies of very low frequency that affect individuals of all ages around the world. All NCLs share a set of symptoms that are similar to other diseases. The exhaustive collection of data from diverse sources (clinical, genetic, neurology, ophthalmology, etc.) would allow being able in the future to define this group with greater precision for a more efficient diagnostic and therapeutic approach. Despite the large amount of information worldwide, a detailed study of the characteristics of the NCLs in South America and the Caribbean region (SA&C) has not yet been done. Here, we aim to present and analyse the multidisciplinary evidence from all the SA&C with qualitative weighting and biostatistical evaluation of the casuistry. Seventy-one publications from seven countries were reviewed, and data from 261 individuals (including 44 individuals from the Cordoba cohort) were collected. Each NCL disease, as well as phenotypical and genetic data were described and discussed in the whole group. The CLN2, CLN6, and CLN3 disorders are the most frequent in the region. Eighty-seven percent of the individuals were 10 years old or less at the onset of symptoms. Seizures were the most common symptom, both at onset (51%) and throughout the disease course, followed by language (16%), motor (15%), and visual impairments (11%). Although symptoms were similar in all NCLs, some chronological differences could be observed. Sixty DNA variants were described, ranging from single nucleotide variants to large chromosomal deletions. The diagnostic odyssey was probably substantially decreased after medical education activities promoted by the pharmaceutical industry and parent organizations in some SA&C countries. There is a statistical deviation in the data probably due to the approval of the enzyme replacement therapy for CLN2 disease, which has led to a greater interest among the medical community for the early description of this pathology. As a general conclusion, it became clear in this work that the combined bibliographical/retrospective evaluation approach allowed a general overview of the multidisciplinary components and the epidemiological tendencies of NCLs in the SA&C region.

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“…For example, clinical symptoms such as bradykinesia, rigidity, and tremors characteristic of PD are also found in some of the LSDs, including JNCL (Aberg et al, 2000, Valadares et al, 2011). Further, extensive reports describing astrocyte activation (Schneider and Denaro, 1988, Blunt et al, 1992, Renkawek et al, 1999, Episcopo et al, 2013) and dysfunction in PD, including aberrant autophagy (Osellame et al, 2013), proteasomal defects (Jansen et al, 2014) and neuroinflammation (Tilleux and Hermans, 2007) are also common features of various LSDs (Jesionek-Kupnicka et al, 1997, Pontikis et al, 2004, Vitner et al, 2010b, Di Malta et al, 2012a, b, Burkovetskaya et al, 2014).…”

Section: Similarities Between Lsds and Parkinson’s Diseasementioning

confidence: 99%

Astrocytes and lysosomal storage diseases

Rao

Kielian²

2016

Neuroscience

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Lysosomal storage diseases (LSDs) encompass a wide range of disorders characterized by inborn errors of lysosomal function. The majority of LSDs result from genetic defects in lysosomal enzymes, although some arise from mutations in lysosomal proteins that lack known enzymatic activity. Neuropathological abnormalities are a feature of several LSDs and when severe, represent an important determinant in disease outcome. Glial dysfunction, particularly in astrocytes, is also observed in numerous LSDs and has been suggested to impact neurodegeneration. This review will discuss the potential role of astrocytes in LSDs and highlight the possibility of targeting glia as a beneficial strategy to counteract the neuropathology associated with LSDs.

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Juvenile neuronal ceroid-lipofuscinosis: clinical and molecular investigation in a large family in Brazil

Cited by 9 publications

References 15 publications

A novel MFSD8 mutation in a Russian patient with neuronal ceroid lipofuscinosis type 7: a case report

A novel MFSD8 mutation in a Russian patient with neuronal ceroid lipofuscinosis type 7: a case report

Neuronal ceroid lipofuscinosis in the South American-Caribbean region: An epidemiological overview

Astrocytes and lysosomal storage diseases

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