Childhood neuronal ceroid‐lipofuscinoses in Argentina

Taratuto, Ana Lía; Saccoliti, M.; Sevlever, Gustavo; Ruggieri, Víctor Luis; Arroyo, H; Herrero, M.C. Miranda; Massaro, Mario; Fejerman, Natalio

doi:10.1002/ajmg.1320570207

Cited by 23 publications

(14 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Relatively similar data are reported in the literature [32] with respect to frequency of INCL, LINCL and JNCL. In Italy [33], a Mediterranean population, and in Argentina [34], whose population is predominantly of European descent, the more frequent form seems to be LINCL, representing 63 % and 80 % of NCL cases, respectively. In both populations INCL is very rare.…”

Section: Discussionmentioning

confidence: 95%

Clinicopathological and molecular characterization of neuronal ceroid lipofuscinosis in the Portuguese population

Teixeira¹,

Guimarães²,

Bessa³

et al. 2003

Journal of Neurology

View full text Add to dashboard Cite

A series of 53 Portuguese patients (derived from 43 families) born in the period 1963-1999 have been diagnosed with neuronal ceroid lipofuscinosis (NCL) based on clinicopathological findings. Plotting the cumulative number of new cases per year against the year of birth resulted in a slightly S-shaped curve, with a nearly straight central segment over a period of 14 years (1977-1990) indicating a continuous registration of new cases born during the corresponding time period. In this period the prevalence of overall NCL in the Portuguese population was calculated to be 1.55 per 100.000 live births.Twenty-six patients from 20 unrelated families were further evaluated by combining clinicopathological with biochemical and genetic data. No intra-familial heterogeneity was observed. Four sub-types of childhood NCL were identified: infantile NCL (INCL) with granular osmiophilic inclusions (GROD) and PPT1 deficiency (1/26), classical LINCL with curvilinear (CV) inclusions and tripeptidyl peptidase (TPP1) deficiency (3/26), variant late infantile NCL (LINCL) with fingerprint/curvilinear (FP/CV) inclusions and normal TPP1 enzyme activity (11/26) and juvenile NCL (JNCL) with a mix of FP/CV (11/26). Eight of 11 JNCL patients were homozygous for the 1.02-kb deletion in the CLN3 gene, and 3 were heterozygous with an unidentified mutation in the second allele. The 1.02-kb deletion in the CLN3 gene accounted for 86.3 % (19/22) of CLN3-causing alleles and 36.5 % (19/52) of childhood NCL defects. The causal mutations for CLN1 and CLN2 were V181M (2/2) and R208X (4/6), respectively. CLN1, CLN2 and CLN3 affected 3.8 %, 11.5 % and 42.3 % of NCL Portuguese patients, respectively. In 42.3 % of patients affected by the vLINCL form, CLN3, CLN5 and CLN8 gene defects were excluded by direct sequencing of cDNA. Genetic variants such as CLN6 might therefore cause a significant portion of childhood NCL in the Portuguese population. The relative frequency of classical childhood forms of NCL in the Portuguese population is reported and contributes to the knowledge of genetic epidemiology of these world-widely distributed disorders.

show abstract

Section: Discussionmentioning

confidence: 95%

Clinicopathological and molecular characterization of neuronal ceroid lipofuscinosis in the Portuguese population

Teixeira¹,

Guimarães²,

Bessa³

et al. 2003

Journal of Neurology

View full text Add to dashboard Cite

show abstract

“…The occurrence of 30 cases of NCL disorders was first published in Argentina by Taratuto et al almost 20 years ago (Taratuto et al, 1995). It was later observed that the disease, caused by mutations in the TPP1/CLN2 gene, is prevalent in the region, and genetic findings were published for CLN1 and CLN2 by our group as part of a systematic detection program implemented in Córdoba, Argentina (Kohan et al, 2005; Noher de Halac et al, 2005; Kohan et al, 2009; Kohan, 2011).…”

Section: Discussionmentioning

confidence: 99%

Neuronal ceroid lipofuscinosis type CLN2: A new rationale for the construction of phenotypic subgroups based on a survey of 25 cases in South America

Kohan

Carabelos

Xin

et al. 2013

Gene

View full text Add to dashboard Cite

Tripeptidyl-peptidase 1 (TPP1) null or residual activity occurs in neuronal ceroid lipofuscinosis (NCL) with underlying TPP1/CLN2 mutations. A survey of 25 South American CLN2 affected individuals enabled the differentiation of two phenotypes: classical late-infantile and variant juvenile, each in approximately 50% of patients, with residual TPP1 activity occurring in approximately 32%. Each individual was assigned to one of three subgroups: (I) n=11, null TPP1 activity in leukocytes; (II) n=8, residual TPP1 activity of 0.60–15.85 nmol/h/mg (nr 110–476); (III) n=6, activity not measured in leukocytes. Curvilinear bodies (CB) appeared in almost all studied CLN2 subjects; the only exceptions occurred in cases of subgroup II: two individuals had combined CBs/fingerprints (FPs), and one case had pure FPs. There were 15 mutations (4 first published in this paper, 3 previously observed in South America by our group, and 8 previously observed by others). In subgroup I, mutations were either missense or nonsense; in subgroups II and III, mutations prevailed at the non-conserved intronic site, c.887-10A>G (intron 7), and to a lesser extent at c.89+5G>C (intron 2), in heterozygous combinations. Grouping phenotypically and genetically known individuals on the basis of TPP1 activity supported the concept that residual enzyme activity underlies a protracted disease course. The prevalence of intronic mutations at nonconserved sites in subgroup II individuals indicates that some alternative splicing might allow some residual TPP1 activity.

show abstract

“…56, 64, 92 The mean age of onset of visual loss has been estimated to be between 6.4-6.6 years, 13, 22 with presentation to an ophthalmologist at 5.5-8.5 years (mean 7.3 years). 22 …”

Section: Clinical Presentationmentioning

confidence: 99%

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) and the Eye

Bozorg

Ramirez-Montealegre

Chung

et al. 2009

Survey of Ophthalmology

View full text Add to dashboard Cite

Juvenile neuronal ceroid lipofuscinoses (JNCL) or Batten disease is the most common type of NCL in the United States and Europe. This devastating disorder presents with vision failure and progresses to include seizures, motor dysfunction, and dementia. Death usually occurs in the third decade, but some patients die before age twenty. Though the mechanism of visual failure remains poorly understood, recent advances in molecular genetics have improved diagnostic testing and suggested possible therapeutic strategies. The ophthalmologist plays a crucial role in both early diagnosis and documentation of progression of JNCL. We update Batten disease research, particularly as it relates to the eye, and present various theories on the pathophysiology of retinal degeneration.

show abstract

Childhood neuronal ceroid‐lipofuscinoses in Argentina

Cited by 23 publications

References 25 publications

Clinicopathological and molecular characterization of neuronal ceroid lipofuscinosis in the Portuguese population

Clinicopathological and molecular characterization of neuronal ceroid lipofuscinosis in the Portuguese population

Neuronal ceroid lipofuscinosis type CLN2: A new rationale for the construction of phenotypic subgroups based on a survey of 25 cases in South America

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) and the Eye

Contact Info

Product

Resources

About