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dc.contributor.authorJerber, Julie
dc.contributor.authorZaki, Maha S.
dc.contributor.authorAl-Aama, Jumana Y.
dc.contributor.authorRosti, Rasim Ozgur
dc.contributor.authorBen-Omran, Tawfeg
dc.contributor.authorDikoglu, Esra
dc.contributor.authorGleeson, Joseph G.
dc.date.accessioned2019-08-13T12:10:23Z
dc.date.accessioned2019-08-13T15:56:52Z
dc.date.available2019-08-13T12:10:23Z
dc.date.available2019-08-13T15:56:52Z
dc.date.issued2016
dc.identifier.issn0002-9297
dc.identifier.issn1537-6605
dc.identifier.urihttps://dx.doi.org/10.1016/j.ajhg.2016.09.007
dc.identifier.urihttp://hdl.handle.net/11446/2402
dc.descriptionWOS: 000387529600015en_US
dc.descriptionPubMed ID: 27773428en_US
dc.description.abstractCobblestone lissencephaly (COB) is a severe brain malformation in which overmigration of neurons and glial cells into the arachnoid space results in the formation of cortical dysplasia. COB occurs in a wide range of genetic disorders known as dystroglycanopathies, which are congenital muscular dystrophies associated with brain and eye anomalies and range from Walker-Warburg syndrome to Fukuyama congenital muscular dystrophy. Each of these conditions has been associated with alpha-dystroglycan defects or with mutations in genes encoding basement membrane components, which are known to interact with alpha-dystroglycan. Our screening of a cohort of 25 families with recessive forms of COB identified six families affected by biallelic mutations in TMTC3 (encoding transmembrane and tetratricopeptide repeat containing 3), a gene without obvious functional connections to alpha-dystroglycan. Most affected individuals showed brainstem and cerebellum hypoplasia, as well as ventriculomegaly. However, the minority of the affected individuals had eye defects or elevated muscle creatine phosphokinase, separating the TMTC3 COB phenotype from typical congenital muscular dystrophies. Our data suggest that loss of TMTC3 causes COB with minimal eye or muscle involvement.en_US
dc.description.sponsorshipFrancois Wallace Mohanan fellowship; NIH [R01GM077243, R01NS041537, R01NS048453, R01NS052455, P01HD070494]; Deutsche Forschungsgemeinschaft [AB393/2-1, AB393/2-2]; Simons Foundation Autism Research Initiative; Qatar National Research Fund [6-1463]; Paul D. Wellstone Muscular Dystrophy Cooperative Research Center [1U54NS053672]en_US
dc.description.sponsorshipWe thank the children and their families for their contributions to this study. This work was supported by the Francois Wallace Mohanan fellowship (J.J.); NIH grant R01GM077243 (J.A.-A.); Deutsche Forschungsgemeinschaft grants AB393/2-1 and AB393/2-2 (R.A.J.); NIH grants R01NS041537, R01NS048453, R01NS052455, and P01HD070494, the Simons Foundation Autism Research Initiative, and Qatar National Research Fund grant 6-1463 (T.B.-O., M.A., and J.G.G.); and Paul D. Wellstone Muscular Dystrophy Cooperative Research Center grant 1U54NS053672 (K.P.C.). K.P.C. and J.G.G. are Howard Hughes Medical Institute Investigators. We thank the Broad Institute (U54HG003067 to E. Lander and UM1HG008900 to D. MacArthur), the Yale Center for Mendelian Disorders (U54HG006504 to R. Lifton and M.G.), and the Gregory M. Kiez and Mehmet Kutman Foundation (M.G.). We acknowledge M. Gerstein, S. Mane, A.B. Ekici, and S. Uebe; the Yale Biomedical High Performance Computing Center for data analysis and storage; the Yale Program on Neurogenetics; and the Yale Center for Human Genetics and Genomics.en_US
dc.language.isoengen_US
dc.publisherCELL PRESSen_US
dc.relation.isversionof10.1016/j.ajhg.2016.09.007en_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.titleBiallelic Mutations in TMTC3, Encoding a Transmembrane and TPR-Containing Protein, Lead to Cobblestone Lissencephalyen_US
dc.typearticleen_US
dc.relation.journalAMERICAN JOURNAL OF HUMAN GENETICSen_US
dc.contributor.departmentDBÜen_US
dc.identifier.issue5en_US
dc.identifier.volume99en_US
dc.identifier.startpage1181en_US
dc.identifier.endpage1189en_US
dc.contributor.authorID0000-0001-7840-0002en_US
dc.contributor.authorID0000-0002-1542-1399en_US
dc.contributor.authorID0000-0003-2066-5889en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US


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