Searching for genomic variants in IGF2 and CDKN1C in Silver-Russell syndrome patients.

摘要

Silver-Russell syndrome (SRS) is a heterogeneous syndrome with evidence for a substantial role of genetic factors in its etiology. Apart from other specific clinical features, severe intrauterine and postnatal growth retardation are the dominant characteristics of SRS. Therefore, studies on the genetic basis of the disease focus on genes involved in growth and its regulation. Another key for the identification of (a) SRS gene(s) is the finding of chromosomal disturbances in SRS patients: recently, four growth retarded patients carrying duplications in 11p15 of maternal origin have been described, two of these cases presented SRS-like features. The same region includes IGF2 and CDKN1C and is well known to harbour alterations in patients suffering from Beckwith-Wiedemann syndrome. We therefore decided to perform an extensive search for variants in the IGF2 and CDKN1C genes; mutations in these genes cause growth disturbances. More than 40 SRS patients were screened for mutations by different detection strategies, allele frequencies were compared between patients and controls. In both genes, we did not detect any obvious pathogenic mutation. In case of IGF2, slight differences in the allelic distribution of specific polymorphisms between SRS patients and controls were observed. In CDKN1C, several variants could be identified in both cohorts with similar frequencies, but only one patient showed a so far unknown variant not detectable in controls.