Screening for genomic variants in ZFP57 in Silver-Russell syndrome patients with 11p15 epimutations.

Silver-Russell syndrome (SRS) describes a uniform malformation syndrome characterized by intrauterine and postnatal growth restriction and morphological abnormalities including a small triangular face, relative macrocephaly, asymmetry of the head and limbs, and clinodactyly V. In >38% of SRS cases a hypomethylation of the H19/IGF2 DMR in 11p15 can be detected. Recently, ZFP57 mutations have been identified as a cause of hypomethylation of multiple imprinted loci. To determine whether ZFP57 mutations influence the H19/IGF2 DMR we screened 30 SRS patients with 11p15-hypomethylation for mutations within the coding region of this gene. Thereby homozygosity for a novel variant in exon 6 of ZFP57 was detected in one patient. Heterozygosity for this variant was found in the patients' parents as well as in 2.5% of healthy controls. Except this new and probably apathogenic polymorphism and some registered SNPs no further variants were detected. In conclusion, this study does not provide evidence that ZFP57 mutations are the cause of 11p15-hypomethylation in SRS patients and contribute to the aetiology of SRS.