Department of Medical Genetics; University of Helsinki
Maternal UPD of human chromosome 7 (matUPD7) is observed in approximately 10% of Silver-Russell syndrome (SRS) cases. SRS represents an extreme syndrome of intrauterine growth retardation (IUGR) and slight dysmorphic signs. In addition, matUPD7 has been reported in patients with only slight dysmorphic features and prenatal or postnatal growth retardation. We have studied the role of matUPD7 in growth failure of unknown etiology and in cases of SRS, and also evaluated the efficiency of genetic testing for matUPD7 as a diagnostic tool. DNA samples were studied from 205 children, 92 girls and 113 boys, with short stature of unknown etiology and their parents. The patient cohort included 39 cases of SRS, 91 patients with intrauterine growth retardation (IUGR) and subsequent postnatal short stature, and 75 patients with postnatal growth retardation only. MatUPD7 was screened for by genotyping 13 chromosome 7 specific microsatellite markers by PCR and an automated sequencer (ABI). Clinical data was obtained from medical records. Six matUPD7 cases were observed (3%, 6/205), exclusively among 39 SRS patients (15%, 6/39) studied. Patients with IUGR and/or postnatal growth retardation and with dysmorphic features did not reveal cases of matUPD7. Our results indicate that matUPD7 cases are predominantly observed among patients meeting the criteria of SRS, and matUPD7 is not a common cause for growth retardation. All six matUPD7 patients have very mild SRS features and they all present with additional characteristics not regarded as typical of SRS; excessive sweating and severe feeding difficulties, starting from infancy and continuing throughout childhood, and speech delay. Cases of matUPD7 seem to form a distinct entity among SRS patients. Furthermore, segmental matUPD7 confined to 7q31-qter in one SRS patient delineates the candidate region for imprinted genes in the etiology of SRS. This matUPD7 segment includes two imprinted genes PEG1/MEST and gamma2-COP, both at 7q32, thus rendering further interest in their roles in SRS. We suggest that screening for matUPD7 should be focused on children with severe pre-and postnatal growth retardation, features indicative of SRS, speech difficulties, and poor feeding.