Mutations in the very low-density lipoprotein receptor VLDLR cause cerebellar hypoplasia and quadrupedal locomotion in humans

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dc.citation.epage4236en_US
dc.citation.issueNumber11en_US
dc.citation.spage4232en_US
dc.citation.volumeNumber105en_US
dc.contributor.authorOzcelik, T.en_US
dc.contributor.authorAkarsu, N.en_US
dc.contributor.authorUz, E.en_US
dc.contributor.authorCaglayan, S.en_US
dc.contributor.authorGulsuner, S.en_US
dc.contributor.authorOnat, O. E.en_US
dc.contributor.authorTan, M.en_US
dc.contributor.authorTan, U.en_US
dc.date.accessioned2016-02-08T10:09:48Z
dc.date.available2016-02-08T10:09:48Z
dc.date.issued2008en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.departmentInstitute of Materials Science and Nanotechnology (UNAM)en_US
dc.description.abstractQuadrupedal gait in humans, also known as Unertan syndrome, is a rare phenotype associated with dysarthric speech, mental retardation, and varying degrees of cerebrocerebellar hypoplasia. Four large consanguineous kindreds from Turkey manifest this phenotype. In two families (A and D), shared homozygosity among affected relatives mapped the trait to a 1.3-Mb region of chromosome 9p24. This genomic region includes the VLDLR gene, which encodes the very low-density lipoprotein receptor, a component of the reelin signaling pathway involved in neuroblast migration in the cerebral cortex and cerebellum. Sequence analysis of VLDLR revealed nonsense mutation R257X in family A and single-nucleotide deletion c2339delT in family D. Both these mutations are predicted to lead to truncated proteins lacking transmembrane and signaling domains. In two other families (B and C), the phenotype is not linked to chromosome 9p. Our data indicate that mutations in VLDLR impair cerebrocerebellar function, conferring in these families a dramatic influence on gait, and that hereditary disorders associated with quadrupedal gait in humans are genetically heterogeneous.en_US
dc.identifier.doi10.1073/pnas.0710010105en_US
dc.identifier.issn1091-6490
dc.identifier.urihttp://hdl.handle.net/11693/23165
dc.language.isoEnglishen_US
dc.publisherNational Academy of Sciencesen_US
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.0710010105en_US
dc.source.titleProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subjectGeneticsen_US
dc.subjectUnertan syndromeen_US
dc.subjectmembrane proteinen_US
dc.subjectnucleotideen_US
dc.subjectreelinen_US
dc.subjectvery low density lipoprotein receptoren_US
dc.subjectadulten_US
dc.subjectageden_US
dc.subjectarticleen_US
dc.subjectbrain cortexen_US
dc.subjectbrain functionen_US
dc.subjectcell migrationen_US
dc.subjectcerebellumen_US
dc.subjectcerebellum hypoplasiaen_US
dc.subjectchromosome 9pen_US
dc.subjectchromosome 9p24en_US
dc.subjectfamilyen_US
dc.subjectfemaleen_US
dc.subjectgaiten_US
dc.subjectgait disorderen_US
dc.subjectgeneen_US
dc.subjectgene mappingen_US
dc.subjectgene mutationen_US
dc.subjectgenetic disorderen_US
dc.subjectgenetic traiten_US
dc.subjectgenomicsen_US
dc.subjecthomozygosityen_US
dc.subjecthumanen_US
dc.subjectmaleen_US
dc.subjectneuroblasten_US
dc.subjectnonsense mutationen_US
dc.subjectnucleotide sequenceen_US
dc.subjectphenotypeen_US
dc.subjectpredictionen_US
dc.subjectpriority journalen_US
dc.subjectprotein domainen_US
dc.subjectquadruped gaiten_US
dc.subjectrelativeen_US
dc.subjectsequence analysisen_US
dc.subjectTurkey (republic)en_US
dc.titleMutations in the very low-density lipoprotein receptor VLDLR cause cerebellar hypoplasia and quadrupedal locomotion in humansen_US
dc.typeArticleen_US

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Department of Molecular Biology and Genetics
Institute of Materials Science and Nanotechnology (UNAM)