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

Two common mutations in the CLN2 gene underlie late infantile neuronal ceroid lipoluscinosis Zhong N, Wisniewski KE, Hartikainen J, Ju W, Moroziewicz DN, McLendon L, Sklower Brooks S, Brown WT. Two common mutations in the CLN2 gene underlie late infantile neuronal ceroid lipofuscinosis 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 ho-mozygote 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Genetics Wiley

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

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References (17)

Publisher
Wiley
Copyright
1998 Blackwell Munksgaard
ISSN
0009-9163
eISSN
1399-0004
DOI
10.1111/j.1399-0004.1998.tb04291.x
Publisher site
See Article on Publisher Site

Abstract

Zhong N, Wisniewski KE, Hartikainen J, Ju W, Moroziewicz DN, McLendon L, Sklower Brooks S, Brown WT. Two common mutations in the CLN2 gene underlie late infantile neuronal ceroid lipofuscinosis 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 ho-mozygote 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.

Journal

Clinical Genetics – Wiley

Published: Sep 1, 1998

Keywords: late infantile onset; mdecular arialysis; mutation; mutation frequency; neuronal ceroid lipofuscinosis

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