Preferential paternal origin of microdeletions caused by prezygotic chromosome or chromatid rearrangements in Sotos syndrome.
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.
Miyake
Noriko
N
Departments of Human Genetics and Pediatrics, Nagasaki University School of Medicine, Nagasaki; and CREST, Japan Science and Technology Corporation, Kawaguchi, Japan.
Kurotaki
Naohiro
N
Sugawara
Hirobumi
H
Shimokawa
Osamu
O
Harada
Naoki
N
Kondoh
Tatsuro
T
Tsukahara
Masato
M
Ishikiriyama
Satoshi
S
Sonoda
Tohru
T
Miyoshi
Yoko
Y
Sakazume
Satoru
S
Fukushima
Yoshimitsu
Y
Ohashi
Hirofumi
H
Nagai
Toshiro
T
Kawame
Hiroshi
H
Kurosawa
Kenji
K
Touyama
Mayumi
M
Shiihara
Takashi
T
Okamoto
Nobuhiko
N
Nishimoto
Junji
J
Yoshiura
Ko-ichiro
K
Ohta
Tohru
T
Kishino
Tatsuya
T
Niikawa
Norio
N
Matsumoto
Naomichi
N
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
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human