Human Genetics

, Volume 123, Issue 3, pp 237–245

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
Original Investigation

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.

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Ali Jalali
    • 1
    • 14
  • Kimberly A. Aldinger
    • 6
  • Ajit Chary
    • 2
  • David G. Mclone
    • 3
  • Robin M. Bowman
    • 3
  • Luan Cong Le
    • 8
  • Phillip Jardine
    • 9
  • Ruth Newbury-Ecob
    • 10
  • Andrew Mallick
    • 11
  • Nadereh Jafari
    • 4
  • Eric J. Russell
    • 5
  • John Curran
    • 5
  • Pam Nguyen
    • 5
  • Karim Ouahchi
    • 12
  • Charles Lee
    • 12
  • William B. Dobyns
    • 7
  • Kathleen J. Millen
    • 7
  • Joao M. Pina-Neto
    • 13
  • John A. Kessler
    • 1
  • Alexander G. Bassuk
    • 1
    • 2
  1. 1.Department of NeurologyNorthwestern University Feinberg School of MedicineChicagoUSA
  2. 2.Department of PediatricsNorthwestern University Feinberg School of MedicineChicagoUSA
  3. 3.Department of NeurosurgeryNorthwestern University Feinberg School of MedicineChicagoUSA
  4. 4.Center for Genetic MedicineNorthwestern University Feinberg School of MedicineChicagoUSA
  5. 5.Department of RadiologyNorthwestern University Feinberg School of MedicineChicagoUSA
  6. 6.Committee on NeurobiologyThe University of ChicagoChicagoUSA
  7. 7.Departments of Human Genetics and NeurologyThe University of ChicagoChicagoUSA
  8. 8.HoChiMinh City HospitalHoChiMinh CityVietnam
  9. 9.Department of PaediatricsBristol Royal Hospital for ChildrenBristolUK
  10. 10.Department of Clinical GeneticsSt Michael’s HospitalBristolUK
  11. 11.Department of PaediatricsYeovil HospitalSomersetUK
  12. 12.Department of PathologyBrigham and Women’s Hospital, Harvard Medical SchoolBostonUK
  13. 13.Department of Genetics, School of MedicineUniversidade de São PaoloRibeirão PretoBrazil
  14. 14.ChicagoUSA

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