Fifty Microdeletions Among 112 Cases of Sotos Syndrome: Low Copy Repeats Possibly Mediate the Common Deletion

Naohiro Kurotaki, Naoki Harada, Osamu Shimokawa, Noriko Miyake, Hiroshi Kawame, Kimiaki Uetake, Yoshio Makita, Tatsuro Kondoh, Tsutomu Ogata, Tomoko Hasegawa, Toshiro Nagai, Takao Ozaki, Mayumi Touyama, Ruthie Shenhav, Hirofumi Ohashi, Livija Medne, Takashi Shiihara, Shigeyuki Ohtsu, Zen Ichiro Kato, Nobuhiko OkamotoJunji Nishimoto, Dorit Lev, Yoko Miyoshi, Satoshi Ishikiriyama, Tohru Sonoda, Satoru Sakazume, Yoshimitsu Fukushima, Kenji Kurosawa, Jan Fang Cheng, Koh Ichiro Yoshiura, Tohru Ohta, Tatsuya Kishino, Norio Niikawa, Naomichi Matsumoto

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111 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)378-387
Number of pages10
JournalHuman mutation
Issue number5
Publication statusPublished - 2003
Externally publishedYes


  • Low copy repeat
  • Microdeletion
  • NSD1
  • SoS
  • Sotos syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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