, Volume 13, Issue 1, pp 31–47 | Cite as

Genotype–phenotype correlation in interstitial 6q deletions: a report of 12 new cases

  • Jill A. Rosenfeld
  • Dina Amrom
  • Eva Andermann
  • Frederick Andermann
  • Martin Veilleux
  • Cynthia Curry
  • Jamie Fisher
  • Stephen Deputy
  • Arthur S. Aylsworth
  • Cynthia M. Powell
  • Kandamurugu Manickam
  • Bryce Heese
  • Melissa Maisenbacher
  • Cathy Stevens
  • Jay W. Ellison
  • Sheila Upton
  • John Moeschler
  • Wilfredo Torres-Martinez
  • Abby Stevens
  • Robert Marion
  • Elaine Maria Pereira
  • Melanie Babcock
  • Bernice Morrow
  • Trilochan Sahoo
  • Allen N. Lamb
  • Blake C. Ballif
  • Alex R. Paciorkowski
  • Lisa G. Shaffer
Original Article


Interstitial deletions of 6q are associated with variable phenotypes, including growth retardation, dysmorphic features, upper limb malformations, and Prader–Willi (PW)-like features. Only a minority of cases in the literature have been characterized with high resolution techniques, making genotype–phenotype correlations difficult. We report 12 individuals with overlapping, 200-kb to 16.4-Mb interstitial deletions within 6q15q22.33 characterized by microarray-based comparative genomic hybridization to better correlate deletion regions with specific phenotypes. Four individuals have a PW-like phenotype, though only two have deletion of SIM1, the candidate gene for this feature. Therefore, other genes on 6q may contribute to this phenotype including multiple genes on 6q16 and our newly proposed candidate, the transcription cofactor gene VGLL2 on 6q22.2. Two individuals present with movement disorders as a major feature, and ataxia is present in a third. The 4.1-Mb 6q22.1q22.2 critical region for movement disorders includes the cerebellar-expressed candidate gene GOPC. Observed brain malformations include thick corpus callosum in two subjects, cerebellar vermal hypoplasia in two subjects, and cerebellar atrophy in one subject. Seven subjects' deletions overlap a ~250-kb cluster of four genes on 6q22.1 including MARCKS, HDAC2, and HS3ST5, which are involved in neural development. Two subjects have only this gene cluster deleted, and one deletion was apparently de novo, suggesting at least one of these genes plays an important role in development. Although the phenotypes associated with 6q deletions can vary, using overlapping deletions to delineate critical regions improves genotype–phenotype correlation for interstitial 6q deletions.


Microarray Prader–Willi-like phenotype Movement disorders Epilepsy Microcephaly 6q deletion 

Supplementary material

10048_2011_306_MOESM1_ESM.pdf (341 kb)
ESM 1(PDF 341 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Jill A. Rosenfeld
    • 1
  • Dina Amrom
    • 2
    • 4
  • Eva Andermann
    • 2
    • 4
    • 5
  • Frederick Andermann
    • 3
    • 4
    • 6
  • Martin Veilleux
    • 3
    • 4
  • Cynthia Curry
    • 7
  • Jamie Fisher
    • 7
  • Stephen Deputy
    • 8
  • Arthur S. Aylsworth
    • 9
    • 10
  • Cynthia M. Powell
    • 9
    • 10
  • Kandamurugu Manickam
    • 9
    • 10
    • 19
  • Bryce Heese
    • 11
    • 20
  • Melissa Maisenbacher
    • 11
  • Cathy Stevens
    • 12
  • Jay W. Ellison
    • 13
    • 21
  • Sheila Upton
    • 14
  • John Moeschler
    • 14
  • Wilfredo Torres-Martinez
    • 15
  • Abby Stevens
    • 15
  • Robert Marion
    • 16
  • Elaine Maria Pereira
    • 16
  • Melanie Babcock
    • 17
  • Bernice Morrow
    • 17
  • Trilochan Sahoo
    • 1
    • 22
  • Allen N. Lamb
    • 1
    • 23
  • Blake C. Ballif
    • 1
  • Alex R. Paciorkowski
    • 18
  • Lisa G. Shaffer
    • 1
  1. 1.Signature Genomic Laboratories, PerkinElmer, Inc.SpokaneUSA
  2. 2.Neurogenetics Unit, Montreal Neurological Hospital & InstituteMontrealCanada
  3. 3.Epilepsy Service, Montreal Neurological Hospital & InstituteMontrealCanada
  4. 4.Department of Neurology & NeurosurgeryMcGill UniversityMontrealCanada
  5. 5.Department of Human GeneticsMcGill UniversityMontrealCanada
  6. 6.Department of PediatricsMcGill UniversityMontrealCanada
  7. 7.Genetic Medicine Central California/UCSFFresnoUSA
  8. 8.Children’s Hospital, New OrleansNew OrleansUSA
  9. 9.Department of PediatricsUniversity of North Carolina, School of MedicineChapel HillUSA
  10. 10.Department of GeneticsUniversity of North Carolina-Chapel HillChapel HillUSA
  11. 11.Shands Hospital at University of FloridaGainesvilleUSA
  12. 12.TC Thompson Children’s HospitalChattanoogaUSA
  13. 13.Mayo ClinicRochesterUSA
  14. 14.Medical Genetics, Children’s Hospital at Dartmouth, Dartmouth Hitchcock Medical CenterLebanonUSA
  15. 15.Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisUSA
  16. 16.Department of Pediatrics, Division of GeneticsChildren’s Hospital at MontefioreBronxUSA
  17. 17.Department of Molecular GeneticsAlbert Einstein College of MedicineBronxUSA
  18. 18.Department of NeurologyUniversity of Washington, and Seattle Children’s Research InstituteSeattleUSA
  19. 19.Nationwide Children’s HospitalColumbusUSA
  20. 20.Children’s Mercy HospitalKansas CityUSA
  21. 21.Signature Genomic Laboratories, PerkinElmer, Inc.SpokaneUSA
  22. 22.Quest Diagnostics Nichols InstituteSan Juan CapistranoUSA
  23. 23.ARUP Laboratories, University of UtahSalt Lake CityUSA

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