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

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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 2008
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgments We would like to thank Hoang Le and Dung Tri Pham, HoChiMinh City Hospital, HoChiMinh City, Vietnam, for their assistance in patient recruitment. A.J. is supported by NIH pre-doctoral NRSA grant F30-NS51962. K.A.A. is supported by NIH Pre-doctoral grant GM007839–26. A.G.B. is supported by NIH grant K08-NS48174.

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