Phenotypic consequences of genetic variation at hemizygous alleles: Sotos syndrome is a contiguous gene syndrome incorporating coagulation factor twelve (FXII) deficiency.
OBJECTIVE
We tested the hypothesis that Sotos syndrome (SoS) due to the common deletion is a contiguous gene syndrome incorporating plasma coagulation factor twelve (FXII) deficiency. The relationship between FXII activity and the genotype at a functional polymorphism of the FXII gene was investigated.


METHODS
A total of 21 patients including those with the common deletion, smaller deletions, and point mutations, and four control individuals were analyzed. We examined FXII activity in patients and controls, and analyzed their FXII 46C/T genotype using direct DNA sequencing.


RESULTS
Among 10 common deletion patients, seven patients had lower FXII activity with the 46T allele of the FXII gene, whereas three patients had normal FXII activity with the 46C allele. Two patients with smaller deletions, whose FXII gene is not deleted had low FXII activity, but one patient with a smaller deletion had normal FXII. Four point mutation patients and controls all had FXII activities within the normal range.


CONCLUSIONS
FXII activity in SoS patients with the common deletion is predominantly determined by the functional polymorphism of the remaining hemizygous FXII allele. Thus, Sotos syndrome is a contiguous gene syndrome incorporating coagulation factor twelve (FXII) deficiency.
Kurotaki
Naohiro
N
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Shen
Joseph J
JJ
Touyama
Mayumi
M
Kondoh
Tatsuro
T
Visser
Remco
R
Ozaki
Takao
T
Nishimoto
Junji
J
Shiihara
Takashi
T
Uetake
Kimiaki
K
Makita
Yoshio
Y
Harada
Naoki
N
Raskin
Salmo
S
Brown
Chester W
CW
Höglund
Pia
P
Okamoto
Nobuhiko
N
Lupski
James R
JR
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D005174:Factor XII / Q000235:genetics / Q000378:metabolism; D005175:Factor XII Deficiency / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D014644:Genetic Variation; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017403:In Situ Hybridization; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation; D013577:Syndrome
D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D005174:Factor XII; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human