title: Linkage to chromosome 2q36.1 in autosomal dominant Dandy-Walker malformation with occipital cephalocele and evidence for genetic heterogeneity.
abstract: We previously reported a Vietnamese-American family with isolated autosomal dominant occipital cephalocele. Upon further neuroimaging studies, we have recharacterized this condition as autosomal dominant Dandy-Walker with occipital cephalocele (ADDWOC). A similar ADDWOC family from Brazil was also recently described. To determine the genetic etiology of ADDWOC, we performed genome-wide linkage analysis on members of the Vietnamese-American and Brazilian pedigrees. Linkage analysis of the Vietnamese-American family identified the ADDWOC causative locus on chromosome 2q36.1 with a multipoint parametric LOD score of 3.3, while haplotype analysis refined the locus to 1.1 Mb. Sequencing of the five known genes in this locus did not identify any protein-altering mutations. However, a terminal deletion of chromosome 2 in a patient with an isolated case of Dandy-Walker malformation also encompassed the 2q36.1 chromosomal region. The Brazilian pedigree did not show linkage to this 2q36.1 region. Taken together, these results demonstrate a locus for ADDWOC on 2q36.1 and also suggest locus heterogeneity for ADDWOC.
authors.affiliation: Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA, ajalali004@md.northwestern.edu
authors.forename: Ali
authors.initials: A
authors.lastname: Jalali
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Aldinger
authors.forename: Ajit
authors.initials: A
authors.lastname: Chary
authors.forename: David G
authors.initials: DG
authors.lastname: McLone
authors.forename: Robin M
authors.initials: RM
authors.lastname: Bowman
authors.forename: Luan Cong
authors.initials: LC
authors.lastname: Le
authors.forename: Phillip
authors.initials: P
authors.lastname: Jardine
authors.forename: Ruth
authors.initials: R
authors.lastname: Newbury-Ecob
authors.forename: Andrew
authors.initials: A
authors.lastname: Mallick
authors.forename: Nadereh
authors.initials: N
authors.lastname: Jafari
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Russell
authors.forename: John
authors.initials: J
authors.lastname: Curran
authors.forename: Pam
authors.initials: P
authors.lastname: Nguyen
authors.forename: Karim
authors.initials: K
authors.lastname: Ouahchi
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Millen
authors.forename: Joao M
authors.initials: JM
authors.lastname: Pina-Neto
authors.forename: John A
authors.initials: JA
authors.lastname: Kessler
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Bassuk
mesh_terms: D002675:Child, Preschool; D002872:Chromosome Deletion; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003616:Dandy-Walker Syndrome / Q000150:complications / Q000235:genetics*; D004677:Encephalocele / Q000150:complications / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics*; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009693:Nucleic Acid Hybridization; D009777:Occipital Bone / Q000002:abnormalities*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*