title: Preferential paternal origin of microdeletions caused by prezygotic chromosome or chromatid rearrangements in Sotos syndrome.
abstract: 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.
authors.affiliation: Departments of Human Genetics and Pediatrics, Nagasaki University School of Medicine, Nagasaki; and CREST, Japan Science and Technology Corporation, Kawaguchi, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kurotaki
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Sugawara
authors.forename: Osamu
authors.initials: O
authors.lastname: Shimokawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Harada
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Kondoh
authors.forename: Masato
authors.initials: M
authors.lastname: Tsukahara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishikiriyama
authors.forename: Tohru
authors.initials: T
authors.lastname: Sonoda
authors.forename: Yoko
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: Satoru
authors.initials: S
authors.lastname: Sakazume
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Fukushima
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohashi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Nagai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawame
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
authors.forename: Mayumi
authors.initials: M
authors.lastname: Touyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiihara
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.forename: Junji
authors.initials: J
authors.lastname: Nishimoto
authors.forename: Ko-ichiro
authors.initials: K
authors.lastname: Yoshiura
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohta
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kishino
authors.forename: Norio
authors.initials: N
authors.lastname: Niikawa
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics; D002842:Chromatids / Q000235:genetics*; D002869:Chromosome Aberrations; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D005260:Female; D005528:Foot / Q000254:growth & development; D005532:Foot Deformities, Congenital / Q000235:genetics; D018392:Genomic Imprinting; D006225:Hand / Q000254:growth & development; D006228:Hand Deformities, Congenital / Q000235:genetics; D006239:Haplotypes; D006257:Head / Q000002:abnormalities / Q000254:growth & development; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009035:Mothers; D009687:Nuclear Proteins / Q000235:genetics; D010334:Paternity; D010375:Pedigree; D017384:Sequence Deletion; D013577:Syndrome
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human