Show simple item record

dc.contributor.authorOnat, Onur Emreen_US
dc.contributor.authorGülsüner, Süleymanen_US
dc.contributor.authorBilgen, R.en_US
dc.contributor.authorDal, G. M.en_US
dc.contributor.authorBilguvar, K.en_US
dc.contributor.authorBoyacı, Hüseyinen_US
dc.contributor.authorDoerschner, Katjaen_US
dc.contributor.authorUysal, H.en_US
dc.contributor.authorGünel, M.en_US
dc.contributor.authorÖzçelik, Tayfunen_US
dc.coverage.spatialSan Francisco, CA, USAen_US
dc.date.accessioned2019-07-09T06:08:12Z
dc.date.available2019-07-09T06:08:12Z
dc.date.issued2012-11en_US
dc.identifier.urihttp://hdl.handle.net/11693/52155
dc.descriptionConference Name: 62nd Annual Meeting of the American Society of Human Genetics, ASHG 2012en_US
dc.descriptionDate of Conference: 06-10 November 2012en_US
dc.description.abstractCongenital mirror movements (CMM) are a rare and heterogeneous group of disorders characterized by involuntary contralateral movements of mainly the upper extremities during intentional movements on the opposite side. Isolated cases are usually familial and suggest autosomal dominant inheritance with incomplete penetrance. In two chromosome 18 linked families, causative mutations were identified in DCC (Science 328:592, 2010; MRMV1; MIM:157600). Here, we describe a three-generation consanguineous Turkish family with six members affected by CMM. Linkage analysis with a dominant model and 90 percent penetrance parameters resulted in peaks on 15q13.3-q21.1, 15q26.2, and 19q12 with maximum multipoint LOD scores of 3.6, 2.6, and 2.6, respectively. However, a region of homozygosity segregating with the phenotype was not observed, and thus excluded the possibility of recessive inheritance of the disease allele in this consanguineous family. Whole-exome sequencing of an affected individual uncovered 7 coding, 33 intronic and 3 intergenic novel variants located within the three linkage intervals, which were filtered against the dbSNP132 dataset. Segregation analysis, population filtering using 1000 genomes and EVS data sets, and conservation considerations using prediction tools revealed a novel missense mutation (c.404C>T [p.T134N], RefSeq accession number NM_002875) in exon 5 of RAD51 (MIM:179617), consistent with the dominant inheritance of the disease allele in the family. The mutation resides in the highly conserved AAA (ATPases associated with diverse cellular activities) domain of the protein, and it was not observed in 436 chromosomes from healthy individuals coming from a geographical matched region. Recently, truncating mutations in RAD51 were identified in two families with CMM (Am J Hum Genet 90:301,2012; MRMV2; MIM:614508). Our findings support the totally unexpected role of RAD51 in neurodevelopment and further suggest that alterations of this gene may lead to neurological phenotypes.en_US
dc.language.isoEnglishen_US
dc.source.title62nd Annual Meeting of the American Society of Human Genetics, ASHG 2012en_US
dc.titleIdentification of a novel missense mutation in RAD51 in a large family with congenital mirror movementsen_US
dc.typeConference Paperen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.departmentDepartment of Psychologyen_US
dc.departmentInstitute of Materials Science and Nanotechnology (UNAM)en_US
dc.departmentNational Magnetic Resonance Research Center (UMRAM)en_US
dc.publisherAmerican Society of Human Geneticsen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record