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 MarionElaine Maria Pereira, Melanie Babcock, Bernice Morrow, Trilochan Sahoo, Allen N. Lamb, Blake C. Ballif, Alex R. Paciorkowski, Lisa G. Shaffer

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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 thisfeature. 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.

Original languageEnglish (US)
Pages (from-to)31-47
Number of pages17
Issue number1
StatePublished - Feb 2012


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

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Cellular and Molecular Neuroscience


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