Human Genetics

, Volume 126, Issue 4, pp 589–602

Redefined genomic architecture in 15q24 directed by patient deletion/duplication breakpoint mapping

  • Ayman W. El-Hattab
  • Teresa A. Smolarek
  • Martha E. Walker
  • Elizabeth K. Schorry
  • LaDonna L. Immken
  • Gayle Patel
  • Mary-Alice Abbott
  • Brendan C. Lanpher
  • Zhishuo Ou
  • Sung-Hae L. Kang
  • Ankita Patel
  • Fernando Scaglia
  • James R. Lupski
  • Sau Wai Cheung
  • Pawel Stankiewicz
Original Investigation

DOI: 10.1007/s00439-009-0706-x

Cite this article as:
El-Hattab, A.W., Smolarek, T.A., Walker, M.E. et al. Hum Genet (2009) 126: 589. doi:10.1007/s00439-009-0706-x

Abstract

We report four new patients with a submicroscopic deletion in 15q24 manifesting developmental delay, short stature, hypotonia, digital abnormalities, joint laxity, genital abnormalities, and characteristic facial features. These clinical features are shared with six recently reported patients with a 15q24 microdeletion, supporting the notion that this is a recognizable syndrome. We describe a case of an ~2.6 Mb microduplication involving a portion of the minimal deletion critical region in a 15-year-old male with short stature, mild mental retardation, attention deficit hyperactivity disorder, Asperger syndrome, decreased joint mobility, digital abnormalities, and characteristic facial features. Some of these features are shared with a recently reported case with a 15q24 microduplication involving the minimal deletion critical region. We also report two siblings and their mother with duplication adjacent and distal to this region exhibiting mild developmental delay, hypotonia, tapering fingers, characteristic facial features, and prominent ears. The deletion and duplication breakpoints were mapped by array comparative genomic hybridization and the genomic structure in 15q24 was analyzed further. Surprisingly, in addition to the previously recognized three low-copy repeat clusters (BP1, BP2, and BP3), we identified two other paralogous low-copy repeat clusters that likely mediated the formation of alternative sized 15q24 genomic rearrangements via non-allelic homologous recombination.

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Ayman W. El-Hattab
    • 1
  • Teresa A. Smolarek
    • 2
  • Martha E. Walker
    • 2
  • Elizabeth K. Schorry
    • 2
  • LaDonna L. Immken
    • 3
  • Gayle Patel
    • 3
  • Mary-Alice Abbott
    • 4
  • Brendan C. Lanpher
    • 5
  • Zhishuo Ou
    • 1
  • Sung-Hae L. Kang
    • 1
  • Ankita Patel
    • 1
  • Fernando Scaglia
    • 1
  • James R. Lupski
    • 1
  • Sau Wai Cheung
    • 1
  • Pawel Stankiewicz
    • 1
    • 6
  1. 1.Department of Molecular and Human GeneticsBaylor College of MedicineHoustonUSA
  2. 2.Division of Human GeneticsCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  3. 3.Clinical Genetics, Specially for ChildrenAustinUSA
  4. 4.Clinical GeneticsBaystate Medical CenterSpringfieldUSA
  5. 5.Division of Genetics and Genomic MedicineVanderbilt UniversityNashvilleUSA
  6. 6.Department of Medical GeneticsInstitute of Mother and ChildWarsawPoland