title: Delineation of a deletion region critical for corpus callosal abnormalities in chromosome 1q43-q44.
abstract: Submicroscopic deletions involving chromosome 1q43-q44 result in cognitive impairment, microcephaly, growth restriction, dysmorphic features, and variable involvement of other organ systems. A consistently observed feature in patients with this deletion are the corpus callosal abnormalities (CCAs), ranging from thinning and hypoplasia to complete agenesis. Previous studies attempting to delineate the critical region for CCAs have yielded inconsistent results. We conducted a detailed clinical and molecular characterization of seven patients with deletions of chromosome 1q43-q44. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. Four patients had CCAs, and shared the smallest region of overlap that contains only three protein coding genes, CEP170, SDCCAG8, and ZNF238. One patient with a small deletion involving SDCCAG8 and AKT3, and another patient with an intragenic deletion of AKT3 did not have any CCA, implying that the loss of these two genes is unlikely to be the cause of CCA. CEP170 is expressed extensively in the brain, and encodes for a protein that is a component of the centrosomal complex. ZNF238 is involved in control of neuronal progenitor cells and survival of cortical neurons. Our results rule out the involvement of AKT3, and implicate CEP170 and/or ZNF238 as novel genes causative for CCA in patients with a terminal 1q deletion.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Sandesh C Sreenath
authors.initials: SC
authors.lastname: Nagamani
authors.forename: Ayelet
authors.initials: A
authors.lastname: Erez
authors.forename: Carolyn
authors.initials: C
authors.lastname: Bay
authors.forename: Anjana
authors.initials: A
authors.lastname: Pettigrew
authors.forename: Seema R
authors.initials: SR
authors.lastname: Lalani
authors.forename: Kristin
authors.initials: K
authors.lastname: Herman
authors.forename: Brett H
authors.initials: BH
authors.lastname: Graham
authors.forename: Malgorzata Jm
authors.initials: MJ
authors.lastname: Nowaczyk
authors.forename: Monica
authors.initials: M
authors.lastname: Proud
authors.forename: William J
authors.initials: WJ
authors.lastname: Craigen
authors.forename: Bobbi
authors.initials: B
authors.lastname: Hopkins
authors.forename: Beth
authors.initials: B
authors.lastname: Kozel
authors.forename: Katie
authors.initials: K
authors.lastname: Plunkett
authors.forename: Patricia
authors.initials: P
authors.lastname: Hixson
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: Ankita
authors.initials: A
authors.lastname: Patel
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
mesh_terms: D000293:Adolescent; D061085:Agenesis of Corpus Callosum / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D055028:Comparative Genomic Hybridization; D005260:Female; D023061:Gene Order; D006801:Humans; D007223:Infant; D008297:Male