PUF60-SCRIB fusion transcript in a patient with 8q24.3 microdeletion and atypical Verheij syndrome

Eur J Med Genet. 2019 Dec;62(12):103587. doi: 10.1016/j.ejmg.2018.11.021. Epub 2018 Nov 23.

Abstract

Expression of the fusion genes is considered to be an important mechanism of tumorigenesis. However it is hardly ever discussed in relation to the neurodevelopmental disorders. Here we report on an 18-years-old female patient with 13.1 kb deletion of 8q24.3 fusing the 5'-portion of SCRIB with the 3'-portion of PUF60 and presenting with borderline intellectual disability, eye coloboma, short stature, scoliosis, heart defects and interestingly postnatal megalencephaly, in contrast to microcephaly, which is usually associated with 8q24.3 deletion (Verheij syndrome). Using next generation sequencing we mapped the breakpoints at nucleotide resolution and showed that the deletion preserved the reading frame. In contrast to the laborious techniques previously used for the precise mapping of deletion breakpoints, our approach identified an accurate interval very rapidly. We demonstrated the expression of the PUF60-SCRIB fusion gene in patient's cells and suggest that the fusion transcript might be a cause of the atypical clinical presentation.

Keywords: Breakpoint cloning; Gene fusion; Intellectual disability; Long-range PCR; Next generation sequencing.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Chromosome Breakpoints
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 8 / genetics*
  • Coloboma / genetics*
  • Coloboma / pathology
  • Female
  • Gene Fusion*
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Megalencephaly / genetics*
  • Megalencephaly / pathology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • RNA Splicing Factors / genetics
  • RNA Splicing Factors / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Scoliosis / genetics*
  • Scoliosis / pathology
  • Syndrome
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • Membrane Proteins
  • RNA Splicing Factors
  • RNA, Messenger
  • Repressor Proteins
  • SCRIB protein, human
  • Tumor Suppressor Proteins
  • poly-U binding splicing factor 60KDa