Linkage to chromosome 2q36.1 in autosomal dominant Dandy-Walker malformation with occipital cephalocele and evidence for genetic heterogeneity.
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.
Jalali
Ali
A
Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA, ajalali004@md.northwestern.edu
Aldinger
Kimberly A
KA
Chary
Ajit
A
McLone
David G
DG
Bowman
Robin M
RM
Le
Luan Cong
LC
Jardine
Phillip
P
Newbury-Ecob
Ruth
R
Mallick
Andrew
A
Jafari
Nadereh
N
Russell
Eric J
EJ
Curran
John
J
Nguyen
Pam
P
Ouahchi
Karim
K
Lee
Charles
C
Dobyns
William B
WB
Millen
Kathleen J
KJ
Pina-Neto
Joao M
JM
Kessler
John A
JA
Bassuk
Alexander G
AG
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*