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

(9 reference statements)

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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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“…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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“…Of the included studies, eight were clinical studies involving 6894 patients, 2 , 3 , 4 , 5 , 6 , 12 , 13 , 14 nine were genetic studies of 6975 subjects, 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 and five were case reports of patients presenting with both ASD and parkinsonism features. 24 , 25 , 26 , 27 , 28 A summary of the key ideas presented in this review can be found in Fig. 1 .…”

Section: Resultsmentioning

confidence: 99%

Linking autism spectrum disorders and parkinsonism: clinical and genetic association

Shengting

Yau

Tseng

et al. 2023

Ann Clin Transl Neurol

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Background: Autism spectrum disorders (ASD) comprise many complex and clinically distinct neurodevelopmental conditions, with increasing evidence linking them to parkinsonism. Methods: We searched Medline and Embase from inception to 21 March 2022 and reviewed the bibliographies of relevant articles. Studies were screened and reviewed comprehensively by two independent authors. Results: Of 863 references from our search, we included eight clinical studies, nine genetic studies, and five case reports. Regardless of age group, Parkinson's disease (PD) and parkinsonian syndromes were more frequently observed in patients with ASD, though the evidence for increased rates of parkinsonism is less clear for children and adolescents. Parkinsonian features and hypokinetic behavior were common in Rett syndrome, with prevalence estimates ranging from 40% to 80%. Frequently observed parkinsonian features include bradykinesia, rigidity, hypomimia, and gait freezing. PD gene PARK2 copy number variations appear more frequently in ASD cases than controls. Evidence suggests that RIT2 and CD157/BST1 are implicated in ASD and PD, while the evidence for other PD-related genes (DRD2, GPCR37, the SLC gene family, and SMPD1) is less clear. Rare mutations, such as ATP13A2, CLN3, and WDR45, could result in autistic behavior and concomitant parkinsonism. Conclusion:The prevalence of parkinsonism in ASD is substantially greater than in the general population or matched controls. Various PD-associated gene loci, especially PARK2, could confer susceptibility to ASD as well. Important future directions include conducting prospective cohort studies to understand how parkinsonian symptoms may progress, genetic studies to reveal relevant gene loci, and pathophysiologic studies to identify potential therapeutic targets.

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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

Astrocytes and lysosomal storage diseases

Linking autism spectrum disorders and parkinsonism: clinical and genetic association

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