Two common mutations in the CLN2 gene underlie late infantile neuronal ceroid lipofuscinosis

Nan Zhong, Krystyna E. Wisniewski, Jaana Hartikainen, Weina Ju, Dorota N. Moroziewicz, Lucille McLendon, Susan Sklower Brooks, W. Ted Brown

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Late infantile neuronal ceroid lipofuscinosis (LINCL) is one of the most common pediatric neuronal degenerative disorders. A candidate gene underlying this disease, designated CLN2, was recently cloned and the gene product was characterized as a lysosomal pepstatin-insensitive carboxypeptidase (LPIC). Four mutations were identified in CLN2 from three unrelated LINCL individuals. To investigate further the mutation frequency in LINCL, we screened 16 LINCL probands for these four mutations. The previously reported intronic mutation, T523-1 G→C, was found in 56% (9/16) of the cases, of which two were homozygous and accounted for 34% (11/32) of LINCL chromosomes. The previously reported nonsense mutation, 636 C→T leading to R208stop, was found in 31% (5/16) of the cases, including one homozygote and accounted for 19% (6/32) of LINCL chromosomes. Two previously described missense mutations, 1107 T→C and 1108 G→A, were not detected in any of these 16 probands. In total, the two observed mutations, T523-1 G→C and 636 C→T, accounted for 53% (17/32) of LINCL alleles. Thus, one or both mutations were seen in 11 (69%) cases and no mutation has yet been identified in five. Our finding that these two mutations are common in LINCL cases adds further evidence in support of the idea that dysfunction of LPIC underlies LINCL. Positive molecular testing can now complement clinical diagnosis of LPIC and will allow for pre-natal diagnosis for subsequent pregnancies.

Original languageEnglish (US)
Pages (from-to)234-238
Number of pages5
JournalClinical Genetics
Issue number3
StatePublished - Sep 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


  • Late infantile onset
  • Molecular analysis
  • Mutation
  • Mutation frequency
  • Neuronal ceroid lipofuscinosis


Dive into the research topics of 'Two common mutations in the CLN2 gene underlie late infantile neuronal ceroid lipofuscinosis'. Together they form a unique fingerprint.

Cite this