Maternal chromosome 7 hetero/isodisomy in Silver-Russell syndrome and PEG1 biallelic expression

Silver-Russell syndrome (SRS) is characterized by a severe intrauterine and postnatal growth retardation, relative macrocephaly associated with 'mild' facial anomalies. The diagnostic importance of skeletal asymmetry remains controversial. The aetiology of the syndrome is heterogeneous. Maternal uniparental disomy of chromosome 7 (mUPD7) has been reported in approximately 7% of patients, but two carriers of chromosomal abnormalities involving the band 17q25 have also been described. We investigated a clinically selected sample of 20 SRS patients for the presence of mUPD7 using polymorphic microsatellite markers spanning the whole chromosome. Maternal UPD7 was found in only one patient corresponding to an incidence of 5%. The allelic distribution in this patient was consistent with heterodisomy. Segregation analysis of chromosome 14 and 16 showed a biparental contribution in all the 20 patients. Blood RNA from the mUPD7 patient and a normal donor were evaluated for the expression of Paternally Expressed Gene (PEG1), an imprinted gene on chromosome 7q32. Biallelic expression of the gene in adult blood tissues was found in both samples. Our results confirm the causal role of mUPD7 in a minority of SRS patients