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Mutation update: Review of TPP1 gene variants associated with neuronal ceroid lipofuscinosis CLN2 disease

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Mutation update: Review of TPP1 gene variants associated with neuronal ceroid lipofuscinosis CLN2 disease. / Gardner, Emily; Bailey, Mitch; Schulz, Angela; Aristorena, Mikel; Miller, Nicole; Mole, Sara E.

In: HUM MUTAT, Vol. 40, No. 11, 11.2019, p. 1924-1938.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Gardner, E, Bailey, M, Schulz, A, Aristorena, M, Miller, N & Mole, SE 2019, 'Mutation update: Review of TPP1 gene variants associated with neuronal ceroid lipofuscinosis CLN2 disease', HUM MUTAT, vol. 40, no. 11, pp. 1924-1938. https://doi.org/10.1002/humu.23860

APA

Gardner, E., Bailey, M., Schulz, A., Aristorena, M., Miller, N., & Mole, S. E. (2019). Mutation update: Review of TPP1 gene variants associated with neuronal ceroid lipofuscinosis CLN2 disease. HUM MUTAT, 40(11), 1924-1938. https://doi.org/10.1002/humu.23860

Vancouver

Gardner E, Bailey M, Schulz A, Aristorena M, Miller N, Mole SE. Mutation update: Review of TPP1 gene variants associated with neuronal ceroid lipofuscinosis CLN2 disease. HUM MUTAT. 2019 Nov;40(11):1924-1938. https://doi.org/10.1002/humu.23860

Bibtex

@article{927b503693144445b3f7a43df53ff0ec,
title = "Mutation update: Review of TPP1 gene variants associated with neuronal ceroid lipofuscinosis CLN2 disease",
abstract = "Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is an autosomal recessive condition caused by variants in the TPP1 gene, leading to deficient activity of the lysosomal enzyme tripeptidyl peptidase I (TPP1). We update on the spectrum of TPP1 variants associated with CLN2 disease, comprising 131 unique variants from 389 individuals (717 alleles) collected from the literature review, public databases, and laboratory communications. Previously unrecorded individuals were added to the UCL TPP1-specific database. Two known pathogenic variants, c.509-1 G>C and c.622 C>T (p.(Arg208*)), collectively occur in 60% of affected individuals in the sample, and account for 50% of disease-associated alleles. At least 86 variants (66%) are private to single families. Homozygosity occurs in 45% of individuals where both alleles are known (87% of reported individuals). Atypical CLN2 disease, TPP1 enzyme deficiency with disease onset and/or progression distinct from classic late-infantile CLN2, represents 13% of individuals recorded with associated phenotype. NCBI ClinVar currently holds records for 37% of variants collected here. Effective CLN2 disease management requires early diagnosis; however, irreversible neurodegeneration occurs before a diagnosis is typically reached at age 5. Timely classification and public reporting of TPP1 variants is essential as molecular testing increases in use as a first-line diagnostic test for pediatric-onset neurological disease.",
keywords = "Alleles, Aminopeptidases/chemistry, Animals, Biomarkers, Databases, Genetic, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/chemistry, Disease Models, Animal, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Molecular Dynamics Simulation, Mutation, Neuronal Ceroid-Lipofuscinoses/diagnosis, Phenotype, Protein Conformation, Serine Proteases/chemistry, Structure-Activity Relationship",
author = "Emily Gardner and Mitch Bailey and Angela Schulz and Mikel Aristorena and Nicole Miller and Mole, {Sara E}",
note = "{\textcopyright} 2019 The Authors. Human Mutation Published by Wiley Periodicals, Inc.",
year = "2019",
month = nov,
doi = "10.1002/humu.23860",
language = "English",
volume = "40",
pages = "1924--1938",
journal = "HUM MUTAT",
issn = "1059-7794",
publisher = "Wiley-Liss Inc.",
number = "11",

}

RIS

TY - JOUR

T1 - Mutation update: Review of TPP1 gene variants associated with neuronal ceroid lipofuscinosis CLN2 disease

AU - Gardner, Emily

AU - Bailey, Mitch

AU - Schulz, Angela

AU - Aristorena, Mikel

AU - Miller, Nicole

AU - Mole, Sara E

N1 - © 2019 The Authors. Human Mutation Published by Wiley Periodicals, Inc.

PY - 2019/11

Y1 - 2019/11

N2 - Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is an autosomal recessive condition caused by variants in the TPP1 gene, leading to deficient activity of the lysosomal enzyme tripeptidyl peptidase I (TPP1). We update on the spectrum of TPP1 variants associated with CLN2 disease, comprising 131 unique variants from 389 individuals (717 alleles) collected from the literature review, public databases, and laboratory communications. Previously unrecorded individuals were added to the UCL TPP1-specific database. Two known pathogenic variants, c.509-1 G>C and c.622 C>T (p.(Arg208*)), collectively occur in 60% of affected individuals in the sample, and account for 50% of disease-associated alleles. At least 86 variants (66%) are private to single families. Homozygosity occurs in 45% of individuals where both alleles are known (87% of reported individuals). Atypical CLN2 disease, TPP1 enzyme deficiency with disease onset and/or progression distinct from classic late-infantile CLN2, represents 13% of individuals recorded with associated phenotype. NCBI ClinVar currently holds records for 37% of variants collected here. Effective CLN2 disease management requires early diagnosis; however, irreversible neurodegeneration occurs before a diagnosis is typically reached at age 5. Timely classification and public reporting of TPP1 variants is essential as molecular testing increases in use as a first-line diagnostic test for pediatric-onset neurological disease.

AB - Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is an autosomal recessive condition caused by variants in the TPP1 gene, leading to deficient activity of the lysosomal enzyme tripeptidyl peptidase I (TPP1). We update on the spectrum of TPP1 variants associated with CLN2 disease, comprising 131 unique variants from 389 individuals (717 alleles) collected from the literature review, public databases, and laboratory communications. Previously unrecorded individuals were added to the UCL TPP1-specific database. Two known pathogenic variants, c.509-1 G>C and c.622 C>T (p.(Arg208*)), collectively occur in 60% of affected individuals in the sample, and account for 50% of disease-associated alleles. At least 86 variants (66%) are private to single families. Homozygosity occurs in 45% of individuals where both alleles are known (87% of reported individuals). Atypical CLN2 disease, TPP1 enzyme deficiency with disease onset and/or progression distinct from classic late-infantile CLN2, represents 13% of individuals recorded with associated phenotype. NCBI ClinVar currently holds records for 37% of variants collected here. Effective CLN2 disease management requires early diagnosis; however, irreversible neurodegeneration occurs before a diagnosis is typically reached at age 5. Timely classification and public reporting of TPP1 variants is essential as molecular testing increases in use as a first-line diagnostic test for pediatric-onset neurological disease.

KW - Alleles

KW - Aminopeptidases/chemistry

KW - Animals

KW - Biomarkers

KW - Databases, Genetic

KW - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/chemistry

KW - Disease Models, Animal

KW - Genetic Association Studies

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Molecular Dynamics Simulation

KW - Mutation

KW - Neuronal Ceroid-Lipofuscinoses/diagnosis

KW - Phenotype

KW - Protein Conformation

KW - Serine Proteases/chemistry

KW - Structure-Activity Relationship

U2 - 10.1002/humu.23860

DO - 10.1002/humu.23860

M3 - SCORING: Journal article

C2 - 31283065

VL - 40

SP - 1924

EP - 1938

JO - HUM MUTAT

JF - HUM MUTAT

SN - 1059-7794

IS - 11

ER -