Preferential paternal origin of microdeletions caused by prezygotic chromosome or chromatid rearrangements in Sotos syndrome

Noriko Miyake, Naohiro Kurotaki, Hirobumi Sugawara, Osamu Shimokawa, Naoki Harada, Tatsuro Kondoh, Masato Tsukahara, Satoshi Ishikiriyama, Tohru Sonoda, Yoko Miyoshi, Satoru Sakazume, Yoshimitsu Fukushima, Hirofumi Ohashi, Toshiro Nagai, Hiroshi Kawame, Kenji Kurosawa, Mayumi Touyama, Takashi Shiihara, Nobuhiko Okamoto, Junji NishimotoKo Ichiro Yoshiura, Tohru Ohta, Tatsuya Kishino, Norio Niikawa, Naomichi Matsumoto

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)


Sotos syndrome (SoS) is characterized by pre- and postnatal overgrowth with advanced bone age; a dysmorphic face with macrocephaly and pointed chin; large hands and feet; mental retardation; and possible susceptibility to tumors. It has been shown that the major cause of SoS is haploinsufficiency of the NSD1 gene at 5q35, because the majority of patients had either a common microdeletion including NSD1 or a truncated type of point mutation in NSD1. In the present study, we traced the parental origin of the microdeletions in 26 patients with SoS by the use of 16 microsatellite markers at or flanking the commonly deleted region. Deletions in 18 of the 20 informative cases occurred in the paternally derived chromosome 5, whereas those in the maternally derived chromosome were found in only two cases. Haplotyping analysis of the marker loci revealed that the paternal deletion in five of seven informative cases and the maternal deletion in one case arose through an intrachromosomal rearrangement, and two other cases of the paternal deletion involved an interchromosomal event, suggesting that the common microdeletion observed in SoS did not occur through a uniform mechanism but preferentially arose prezygotically.

Original languageEnglish
Pages (from-to)1331-1337
Number of pages7
JournalAmerican Journal of Human Genetics
Issue number5
Publication statusPublished - 2003 May 1
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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