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.