Expanding the genotype-phenotype correlation in subtelomeric 19p13.3 microdeletions using high resolution clinical chromosomal microarray analysis

Sirisha Peddibhotla, Mohamed Khalifa, Frank J. Probst, Jennifer Stein, Leslie L. Harris, Debra L. Kearney, Gail H. Vance, Marilyn J. Bull, Dorothy K. Grange, Gunter H. Scharer, Sue Hae L. Kang, Pawel Stankiewicz, Carlos A. Bacino, Sau W. Cheung, Ankita Patel

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Structural rearrangements of chromosome 19p are rare, and their resulting phenotypic consequences are not well defined. This is the first study to report a cohort of eight patients with subtelomeric 19p13.3 microdeletions, identified using clinical chromosomal microarray analysis (CMA). The deletion sizes ranged from 0.1 to 0.86Mb. Detailed analysis of the patients' clinical features has enabled us to define a constellation of clinical abnormalities that include growth delay, multiple congenital anomalies, global developmental delay, learning difficulties, and dysmorphic facial features. There are eight genes in the 19p13.3 region that may potentially contribute to the clinical phenotype via haploinsufficiency. Moreover, in silico genomic analysis of 19p13.3 microdeletion breakpoints revealed numerous highly repetitive sequences, suggesting LINEs/SINEs-mediated events in generating these microdeletions. Thus, subtelomeric 19p13.3 appears important for normal embryonic and childhood development. The clinical description of patients with deletions in this genomic interval will assist clinicians to identify and treat individuals with similar deletions.

Original languageEnglish (US)
Pages (from-to)2953-2963
Number of pages11
JournalAmerican Journal of Medical Genetics, Part A
Volume161
Issue number12
DOIs
StatePublished - Dec 1 2013

Keywords

  • 19p aberrations
  • 19p13.3 microdeletion
  • Dysmorphic features
  • Genomic microarray
  • Global developmental delay
  • Learning disability
  • Multiple congenital anomalies
  • Subtelomere
  • VACTERL

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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    Peddibhotla, S., Khalifa, M., Probst, F. J., Stein, J., Harris, L. L., Kearney, D. L., Vance, G. H., Bull, M. J., Grange, D. K., Scharer, G. H., Kang, S. H. L., Stankiewicz, P., Bacino, C. A., Cheung, S. W., & Patel, A. (2013). Expanding the genotype-phenotype correlation in subtelomeric 19p13.3 microdeletions using high resolution clinical chromosomal microarray analysis. American Journal of Medical Genetics, Part A, 161(12), 2953-2963. https://doi.org/10.1002/ajmg.a.35886