Molecular epidemiology of childhood neuronal ceroid-lipofuscinosis in Italy

Filippo Maria Santorelli, Barbara Garavaglia, Francesco Cardona, Nardo Nardocci, Bernardo Dalla Bernardina, Stefano Sartori, Agnese Suppiej, Enrico Bertini, Dianela Claps, Roberta Battini, Roberta Biancheri, Mirella Filocamo, Francesco Pezzini, Alessandro Simonati

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: To review the descriptive epidemiological data on neuronal ceroid lipofuscinoses (NCLs) in Italy, identify the spectrum of mutations in the causative genes, and analyze possible genotype-phenotype relations. Methods. A cohort of NCL patients was recruited through CLNet, a nationwide network of child neurology units. Diagnosis was based on clinical and pathological criteria following ultrastructural investigation of peripheral tissues. Molecular confirmation was obtained during the diagnostic procedure or, when possible, retrospectively. Results: One hundred eighty-three NCL patients from 156 families were recruited between 1966 and 2010; 124 of these patients (from 88 families) were tested for known NCL genes, with 9.7% of the patients in this sample having not a genetic diagnosis. Late infantile onset NCL (LINCL) accounted for 75.8% of molecularly confirmed cases, the most frequent form being secondary to mutations in CLN2 (23.5%). Juvenile onset NCL patients accounted for 17.7% of this cohort, a smaller proportion than found in other European countries. Gene mutations predicted severe protein alterations in 65.5% of the CLN2 and 78.6% of the CLN7 cases. An incidence rate of 0.98/100,000 live births was found in 69 NCL patients born between 1992 and 2004, predicting 5 new cases a year. Prevalence was 1.2/1,000,000. Conclusions: Descriptive epidemiology data indicate a lower incidence of NCLs in Italy as compared to other European countries. A relatively high number of private mutations affecting all NCL genes might explain the genetic heterogeneity. Specific gene mutations were associated with severe clinical courses in selected NCL forms only.

Original languageEnglish
Article number19
JournalOrphanet Journal of Rare Diseases
Volume8
Issue number1
DOIs
Publication statusPublished - 2013

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Neuronal Ceroid-Lipofuscinoses
Molecular Epidemiology
Italy
Mutation
Genes
Genetic Heterogeneity
Incidence
Live Birth
Neurology
Epidemiology
Genotype

Keywords

  • Childhood NCL
  • Epidemiology
  • Italy
  • NCL Genes

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

Molecular epidemiology of childhood neuronal ceroid-lipofuscinosis in Italy. / Santorelli, Filippo Maria; Garavaglia, Barbara; Cardona, Francesco; Nardocci, Nardo; Bernardina, Bernardo Dalla; Sartori, Stefano; Suppiej, Agnese; Bertini, Enrico; Claps, Dianela; Battini, Roberta; Biancheri, Roberta; Filocamo, Mirella; Pezzini, Francesco; Simonati, Alessandro.

In: Orphanet Journal of Rare Diseases, Vol. 8, No. 1, 19, 2013.

Research output: Contribution to journalArticle

Santorelli, Filippo Maria ; Garavaglia, Barbara ; Cardona, Francesco ; Nardocci, Nardo ; Bernardina, Bernardo Dalla ; Sartori, Stefano ; Suppiej, Agnese ; Bertini, Enrico ; Claps, Dianela ; Battini, Roberta ; Biancheri, Roberta ; Filocamo, Mirella ; Pezzini, Francesco ; Simonati, Alessandro. / Molecular epidemiology of childhood neuronal ceroid-lipofuscinosis in Italy. In: Orphanet Journal of Rare Diseases. 2013 ; Vol. 8, No. 1.
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abstract = "Background: To review the descriptive epidemiological data on neuronal ceroid lipofuscinoses (NCLs) in Italy, identify the spectrum of mutations in the causative genes, and analyze possible genotype-phenotype relations. Methods. A cohort of NCL patients was recruited through CLNet, a nationwide network of child neurology units. Diagnosis was based on clinical and pathological criteria following ultrastructural investigation of peripheral tissues. Molecular confirmation was obtained during the diagnostic procedure or, when possible, retrospectively. Results: One hundred eighty-three NCL patients from 156 families were recruited between 1966 and 2010; 124 of these patients (from 88 families) were tested for known NCL genes, with 9.7{\%} of the patients in this sample having not a genetic diagnosis. Late infantile onset NCL (LINCL) accounted for 75.8{\%} of molecularly confirmed cases, the most frequent form being secondary to mutations in CLN2 (23.5{\%}). Juvenile onset NCL patients accounted for 17.7{\%} of this cohort, a smaller proportion than found in other European countries. Gene mutations predicted severe protein alterations in 65.5{\%} of the CLN2 and 78.6{\%} of the CLN7 cases. An incidence rate of 0.98/100,000 live births was found in 69 NCL patients born between 1992 and 2004, predicting 5 new cases a year. Prevalence was 1.2/1,000,000. Conclusions: Descriptive epidemiology data indicate a lower incidence of NCLs in Italy as compared to other European countries. A relatively high number of private mutations affecting all NCL genes might explain the genetic heterogeneity. Specific gene mutations were associated with severe clinical courses in selected NCL forms only.",
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AU - Santorelli, Filippo Maria

AU - Garavaglia, Barbara

AU - Cardona, Francesco

AU - Nardocci, Nardo

AU - Bernardina, Bernardo Dalla

AU - Sartori, Stefano

AU - Suppiej, Agnese

AU - Bertini, Enrico

AU - Claps, Dianela

AU - Battini, Roberta

AU - Biancheri, Roberta

AU - Filocamo, Mirella

AU - Pezzini, Francesco

AU - Simonati, Alessandro

PY - 2013

Y1 - 2013

N2 - Background: To review the descriptive epidemiological data on neuronal ceroid lipofuscinoses (NCLs) in Italy, identify the spectrum of mutations in the causative genes, and analyze possible genotype-phenotype relations. Methods. A cohort of NCL patients was recruited through CLNet, a nationwide network of child neurology units. Diagnosis was based on clinical and pathological criteria following ultrastructural investigation of peripheral tissues. Molecular confirmation was obtained during the diagnostic procedure or, when possible, retrospectively. Results: One hundred eighty-three NCL patients from 156 families were recruited between 1966 and 2010; 124 of these patients (from 88 families) were tested for known NCL genes, with 9.7% of the patients in this sample having not a genetic diagnosis. Late infantile onset NCL (LINCL) accounted for 75.8% of molecularly confirmed cases, the most frequent form being secondary to mutations in CLN2 (23.5%). Juvenile onset NCL patients accounted for 17.7% of this cohort, a smaller proportion than found in other European countries. Gene mutations predicted severe protein alterations in 65.5% of the CLN2 and 78.6% of the CLN7 cases. An incidence rate of 0.98/100,000 live births was found in 69 NCL patients born between 1992 and 2004, predicting 5 new cases a year. Prevalence was 1.2/1,000,000. Conclusions: Descriptive epidemiology data indicate a lower incidence of NCLs in Italy as compared to other European countries. A relatively high number of private mutations affecting all NCL genes might explain the genetic heterogeneity. Specific gene mutations were associated with severe clinical courses in selected NCL forms only.

AB - Background: To review the descriptive epidemiological data on neuronal ceroid lipofuscinoses (NCLs) in Italy, identify the spectrum of mutations in the causative genes, and analyze possible genotype-phenotype relations. Methods. A cohort of NCL patients was recruited through CLNet, a nationwide network of child neurology units. Diagnosis was based on clinical and pathological criteria following ultrastructural investigation of peripheral tissues. Molecular confirmation was obtained during the diagnostic procedure or, when possible, retrospectively. Results: One hundred eighty-three NCL patients from 156 families were recruited between 1966 and 2010; 124 of these patients (from 88 families) were tested for known NCL genes, with 9.7% of the patients in this sample having not a genetic diagnosis. Late infantile onset NCL (LINCL) accounted for 75.8% of molecularly confirmed cases, the most frequent form being secondary to mutations in CLN2 (23.5%). Juvenile onset NCL patients accounted for 17.7% of this cohort, a smaller proportion than found in other European countries. Gene mutations predicted severe protein alterations in 65.5% of the CLN2 and 78.6% of the CLN7 cases. An incidence rate of 0.98/100,000 live births was found in 69 NCL patients born between 1992 and 2004, predicting 5 new cases a year. Prevalence was 1.2/1,000,000. Conclusions: Descriptive epidemiology data indicate a lower incidence of NCLs in Italy as compared to other European countries. A relatively high number of private mutations affecting all NCL genes might explain the genetic heterogeneity. Specific gene mutations were associated with severe clinical courses in selected NCL forms only.

KW - Childhood NCL

KW - Epidemiology

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KW - NCL Genes

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