Homozygous deletion of DIS3L2 exon 9 due to non-allelic homologous recombination between LINE-1s in a Japanese patient with Perlman syndrome

Eur J Hum Genet. 2013 Nov;21(11):1316-9. doi: 10.1038/ejhg.2013.45. Epub 2013 Mar 13.


Perlman syndrome is a rare, autosomal recessive overgrowth disorder. Recently, the deletion of exon 9 and other mutations of the DIS3L2 gene have been reported in patients; however, the mechanism behind this deletion is still unknown. We report the homozygous deletion of exon 9 of DIS3L2 in a Japanese patient with Perlman syndrome. We identified the deletion junction, and implicate a non-allelic homologous recombination (NAHR) between two LINE-1 (L1) elements as the causative mechanism. Furthermore, the deletion junctions were different between the paternal and maternal mutant alleles, suggesting the occurrence of two independent NAHR events in the ancestors of each parent. The data suggest that the region around exon 9 might be a hot spot of L1-mediated NAHR.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Asian People / genetics*
  • Base Sequence
  • Exons / genetics*
  • Exoribonucleases / genetics*
  • Fatal Outcome
  • Fetal Macrosomia / genetics*
  • Homologous Recombination / genetics*
  • Homozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Long Interspersed Nucleotide Elements / genetics*
  • Male
  • Molecular Sequence Data
  • Sequence Deletion / genetics*
  • Wilms Tumor / genetics*


  • DIS3L2 protein, human
  • Exoribonucleases

Supplementary concepts

  • Nephroblastomatosis, fetal ascites, macrosomia and Wilms tumor