MOLECULAR STUDIES IN 37 SILVER-RUSSELL-SYNDROME PATIENTS - FREQUENCY AND ETIOLOGY OF UNIPARENTAL DISOMY

We report studies on the etiology of uniparental disomy (UPD) in Silve r-Russell syndrome (SRS) patients. Thirty-seven SRS families were type d with short tandem repeat markers from chromosomes 2, 7, 9, 14, and 1 6. UPD for these chromosomes has either been described in association with growth retardation or has been observed in confined placental mos aicism, a mechanism that may result in UPD. Maternal UPD7 was detected in three SRS patients, accounting for approximately 10% of the tested SRS patients. These results agree with previously published studies. The allelic distribution in one of the three families indicates comple te isodisomy, whereas allelic patterns in the other two families are c onsistent with partial aid complete heterodisomy, respectively, sugges ting that, in the latter cases, UPD originates from maternal meiosis, whereas in the first case, it seems to be of mitotic origin. STR typin g for UPD of chromosomes 2, 9, 14, and 16 showed no abnormalities. Our results demonstrate the necessity of screening SRS patients for UPD7, although the effect of UPD7 cannot be correlated with the SRS phenoty pe as yet. An association between UPD for the other investigated chrom osomes and SRS seems to be negligible.