LOT1 (ZAC1/PLAGL1) as member of an imprinted gene network does not harbor Silver-Russell specific variants.
Silver-Russell syndrome (SRS) is a heterogeneous disease associated with intrauterine and postnatal growth retardation (IUGR/PNGR), asymmetry and craniofacial dysmorphisms. In 7-10% of patients with SRS, maternal uniparental disomy of chromosome 7 can be detected; more than 38% carry hypomethylation of the imprinting region 1 in 11p15. These chromosomes harbor the imprinted genes IGF2, H19, LIT1 and MEST. In mice, interaction of these genes with the prenatally rexpressed Plagl1/Zac1 has been reported. The aim of this study was to identify mutations in the maternally imprinted LOT1(ZAC1/PLAGL1) gene in 6q24 in patients with SRS. We screened 30 patients with SRS and 14 patients with isolated IUGR/PNGR by SSCP and/or direct sequencing. Mutation analysis revealed nine genomic variants. Seven were novel but classified as apathogenic. Interestingly, two of these variants, g.10212T/A and g.10214C/A, showed strict association. However, our results do not indicate a relevant role of mutations in LOT1(ZAC1/PLAGL1) in the etiology of SRS.
Jäger
Susanne
S
Institute of Human Genetics, Aachen, Germany.
Schönherr
Nadine
N
Spengler
Sabrina
S
Ranke
Michael B
MB
Wollmann
Hartmut A
HA
Binder
Gerhard
G
Eggermann
Thomas
T
D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D002897:Chromosomes, Human, Pair 7; D019465:Craniofacial Abnormalities / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005317:Fetal Growth Retardation / Q000235:genetics*; D018392:Genomic Imprinting; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D024182:Uniparental Disomy
D018797:Cell Cycle Proteins; C106464:PLAGL1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins