Fifty microdeletions among 112 cases of Sotos syndrome: low copy repeats possibly mediate the common deletion

Hum Mutat. 2003 Nov;22(5):378-87. doi: 10.1002/humu.10270.


Sotos syndrome (SoS) is an autosomal dominant overgrowth syndrome with characteristic craniofacial dysmorphic features and various degrees of mental retardation. We previously showed that haploinsufficiency of the NSD1 gene is the major cause of SoS, and submicroscopic deletions at 5q35, including NSD1, were found in about a half (20/42) of our patients examined. Since the first report, an additional 70 SoS cases consisting of 53 Japanese and 17 non-Japanese have been analyzed. We found 50 microdeletions (45%) and 16 point mutations (14%) among all the 112 cases. A large difference in the frequency of microdeletions between Japanese and non-Japanese patients was noted: 49 (52%) of the 95 Japanese patients and only one (6%) of the 17 non-Japanese had microdeletions. A sequence-based physical map was constructed to characterize the microdeletions. Most of the microdeletions were confirmed to be identical by FISH analysis. We identified highly homologous sequences, i.e., possible low copy repeats (LCRs), in regions flanking proximal and distal breakpoints of the common deletion, This suggests that LCRs may mediate the deletion. Such LCRs seem to be present in different populations. Thus the different frequency of microdeletions between Japanese and non-Japanese cases in our study may have been caused by patient-selection bias.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 5
  • Craniofacial Abnormalities / genetics*
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Gigantism / genetics*
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Humans
  • In Situ Hybridization, Fluorescence
  • Intellectual Disability / genetics*
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Nuclear Proteins / genetics*
  • Point Mutation
  • Polymorphism, Single Nucleotide
  • Repetitive Sequences, Nucleic Acid
  • Sequence Deletion*
  • Syndrome


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • NSD1 protein, human