Linkage to chromosome 2q36.1 in autosomal dominant Dandy-Walker malformation with occipital cephalocele and evidence for genetic heterogeneity

Ali Jalali*, Kimberly A. Aldinger, Ajit Chary, David G. Mclone, Robin M. Bowman, Luan Cong Le, Phillip Jardine, Ruth Newbury-Ecob, Andrew Mallick, Nadereh Jafari, Eric J. Russell, John Curran, Pam Nguyen, Karim Ouahchi, Charles Lee, William B. Dobyns, Kathleen J. Millen, Joao M. Pina-Neto, John A. Kessler, Alexander G. Bassuk

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)237-245
Number of pages9
JournalHuman Genetics
Volume123
Issue number3
DOIs
StatePublished - Apr 1 2008

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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