The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter

Eija Siintola, Meral Topcu, Nina Aula, Hannes Lohi, Berge A. Minassian, Andrew D. Paterson, Xiao Qing Liu, Callum Wilson, Ulla Lahtinen, Anna Kaisa Anttonen, Anna Elina Lehesjoki

Research output: Contribution to journalArticle

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Abstract

The late-infantile-onset forms are the most genetically heterogeneous group among the autosomal recessively inherited neurodegenerative disorders, the neuronal ceroid lipofuscinoses (NCLs). The Turkish variant was initially considered to be a distinct genetic entity, with clinical presentation similar to that of other forms of late-infantile-onset NCL (LINCL), including age at onset from 2 to 7 years, epileptic seizures, psychomotor deterioration, myoclonus, loss of vision, and premature death. However, Turkish variant LINCL was recently found to be genetically heterogeneous, because mutations in two genes, CLN6 and CLN8, were identified to underlie the disease phenotype in a subset of patients. After a genomewide scan with single-nucleotide-polymorphism markers and homozygosity mapping in nine Turkish families and one Indian family, not linked to any of the known NCL loci, we mapped a novel variant LINCL locus to chromosome 4q28.1-q28.2 in five families. We identified six different mutations in the MFSD8 gene (previously denoted "MGC33302"), which encodes a novel polytopic 518-amino acid membrane protein that belongs to the major facilitator superfamily of transporter proteins. MFSD8 is expressed ubiquitously, with several alternatively spliced variants. Like the majority of the previously identified NCL proteins, MFSD8 localizes mainly to the lysosomal compartment. However, the function of MFSD8 remains to be elucidated. Analysis of the genome-scan data suggests the existence of at least three more genes in the remaining five families, further corroborating the great genetic heterogeneity of LINCLs.

Original languageEnglish (US)
Pages (from-to)136-146
Number of pages11
JournalAmerican Journal of Human Genetics
Volume81
Issue number1
DOIs
StatePublished - Jan 1 2007

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Neuronal Ceroid-Lipofuscinoses
Genes
Mutation
Myoclonus
Premature Mortality
Genetic Heterogeneity
Age of Onset
Neurodegenerative Diseases
Single Nucleotide Polymorphism
Epilepsy
Membrane Proteins
Proteins
Chromosomes
Genome
Phenotype
Amino Acids

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter. / Siintola, Eija; Topcu, Meral; Aula, Nina; Lohi, Hannes; Minassian, Berge A.; Paterson, Andrew D.; Liu, Xiao Qing; Wilson, Callum; Lahtinen, Ulla; Anttonen, Anna Kaisa; Lehesjoki, Anna Elina.

In: American Journal of Human Genetics, Vol. 81, No. 1, 01.01.2007, p. 136-146.

Research output: Contribution to journalArticle

Siintola, E, Topcu, M, Aula, N, Lohi, H, Minassian, BA, Paterson, AD, Liu, XQ, Wilson, C, Lahtinen, U, Anttonen, AK & Lehesjoki, AE 2007, 'The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter', American Journal of Human Genetics, vol. 81, no. 1, pp. 136-146. https://doi.org/10.1086/518902
Siintola, Eija ; Topcu, Meral ; Aula, Nina ; Lohi, Hannes ; Minassian, Berge A. ; Paterson, Andrew D. ; Liu, Xiao Qing ; Wilson, Callum ; Lahtinen, Ulla ; Anttonen, Anna Kaisa ; Lehesjoki, Anna Elina. / The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter. In: American Journal of Human Genetics. 2007 ; Vol. 81, No. 1. pp. 136-146.
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