Homozygosity mapping and targeted genomic sequencing reveal the game responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred

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buir.contributor.authorGulsuner, Süleyman
buir.contributor.authorTekinay, Ayşe Begüm
buir.contributor.authorDoerschner, Katja
buir.contributor.authorBoyaci, Hüseyin
buir.contributor.authorÜnal, Hilal
buir.contributor.authorÖrs, Aslıhan
buir.contributor.authorOnat, O. Emre
buir.contributor.authorAtalar, Ergin
buir.contributor.authorÖzçelik, Tayfun
dc.citation.epage2003en_US
dc.citation.spage1995en_US
dc.citation.volumeNumber21en_US
dc.contributor.authorGulsuner, Süleymanen_US
dc.contributor.authorTekinay, Ayşe Begümen_US
dc.contributor.authorDoerschner, Katjaen_US
dc.contributor.authorBoyaci, Hüseyinen_US
dc.contributor.authorBilguvar, K.en_US
dc.contributor.authorÜnal, Hilalen_US
dc.contributor.authorÖrs, Aslıhanen_US
dc.contributor.authorOnat, O. Emreen_US
dc.contributor.authorAtalar, Erginen_US
dc.contributor.authorBasak, A. N.en_US
dc.contributor.authorTopaloglu, H.en_US
dc.contributor.authorKansu, T.en_US
dc.contributor.authorTan, M.en_US
dc.contributor.authorTan, U.en_US
dc.contributor.authorGunel, M.en_US
dc.contributor.authorÖzçelik, Tayfunen_US
dc.date.accessioned2015-07-28T12:00:18Z
dc.date.available2015-07-28T12:00:18Z
dc.date.issued2011en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.departmentInstitute of Materials Science and Nanotechnology (UNAM)en_US
dc.departmentDepartment of Psychologyen_US
dc.departmentNational Magnetic Resonance Research Center (UMRAM)en_US
dc.departmentDepartment of Electrical and Electronics Engineeringen_US
dc.departmentNanotechnology Research Center (NANOTAM)en_US
dc.departmentAysel Sabuncu Brain Research Center (BAM)en_US
dc.description.abstractThe biological basis for the development of the cerebro-cerebellar structures required for posture and gait in humans is poorly understood. We investigated a large consanguineous family from Turkey exhibiting an extremely rare phenotype associated with quadrupedal locomotion, mental retardation, and cerebro-cerebellar hypoplasia, linked to a 7.1-Mb region of homozygosity on chromosome 17p13.1-13.3. Diffusion weighted imaging and fiber tractography of the patients' brains revealed morphological abnormalities in the cerebellum and corpus callosum, in particular atrophy of superior, middle, and inferior peduncles of the cerebellum. Structural magnetic resonance imaging showed additional morphometric abnormalities in several cortical areas, including the corpus callosum, precentral gyrus, and Brodmann areas BA6, BA44, and BA45. Targeted sequencing of the entire homozygous region in three affected individuals and two obligate carriers uncovered a private missense mutation, WDR81 p.P856L, which cosegregated with the condition in the extended family. The mutation lies in a highly conserved region of WDR81, flanked by an N-terminal BEACH domain and C-terminal WD40 beta-propeller domains. WDR81 is predicted to be a transmembrane protein. It is highly expressed in the cerebellum and corpus callosum, in particular in the Purkinje cell layer of the cerebellum. WDR81 represents the third gene, after VLDLR and CA8, implicated in quadrupedal locomotion in humans.en_US
dc.identifier.doi10.1101/gr.126110.111en_US
dc.identifier.issn1088-9051
dc.identifier.urihttp://hdl.handle.net/11693/12160
dc.language.isoEnglishen_US
dc.publisherCold Spring Harbor Laboratory Pressen_US
dc.relation.isversionofhttp://dx.doi.org/10.1101/gr.126110.111en_US
dc.source.titleGenome Researchen_US
dc.titleHomozygosity mapping and targeted genomic sequencing reveal the game responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindreden_US
dc.typeArticleen_US
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Department of Molecular Biology and Genetics
Aysel Sabuncu Brain Research Center (BAM)
Department of Electrical and Electronics Engineering
Department of Psychology
Institute of Materials Science and Nanotechnology (UNAM)
Nanotechnology Research Center (NANOTAM)
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