Clinical and genomic characterization of 8p cytogenomic disorders

Genet Med. 2021 Dec;23(12):2342-2351. doi: 10.1038/s41436-021-01270-2. Epub 2021 Jul 19.

Abstract

Purpose: To provide a detailed clinical and cytogenomic summary of individuals with chromosome 8p rearrangements of invdupdel(8p), del(8p), and dup(8p).

Methods: We enrolled 97 individuals with invdupdel(8p), del(8p), and dup(8p). Clinical and molecular data were collected to delineate and compare the clinical findings and rearrangement breakpoints. We included additional 5 individuals with dup(8p) from the literature for a total of 102 individuals.

Results: Eighty-one individuals had recurrent rearrangements of invdupdel(8p) (n = 49), del(8p)_distal (n = 4), del(8p)_proximal (n = 9), del(8p)_proximal&distal (n = 12), and dup(8p)_proximal (n = 7). Twenty-one individuals had nonrecurrent rearrangements. While all individuals had neurodevelopmental features, the frequency and severity of clinical findings were higher in individuals with invdupdel(8p), and with larger duplications. All individuals with GATA4 deletion had structural congenital heart defects; however, the presence of structural heart defects in some individuals with normal GATA4 copy number suggests there are other potentially contributing gene(s) on 8p.

Conclusion: Our study may inform families and health-care providers about the associated clinical findings and severity in individuals with chromosome 8p rearrangements, and guide researchers in investigating the underlying molecular and biological mechanisms by providing detailed clinical and cytogenomic information about individuals with distinct 8p rearrangements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Deletion*
  • Chromosome Inversion*
  • Genomics
  • Humans
  • In Situ Hybridization, Fluorescence