Is maternal duplication of 11p15 associated with Silver-Russell syndrome?. Issue 5 (29th April 2005)

• Record Type: Journal Article
• Authors: Eggermann, T; Meyer, E; Obermann, C; Heil, I; Schüler, H; Ranke, M B; Eggermann, K; Wollmann, H A
• Is Part Of: Journal of medical genetics. Volume 42:Issue 5(2005)
• Page Start: e26
• Page End: e26
• Publication Date: 2005-04-29
• Subjects: BWS, Beckwith-Wiedemann syndrome -- IUGR, intrauterine growth retardation -- PGR, postnatal growth retardation -- rhGH, recombinant human growth hormone -- SRS, Silver-Russell syndrome -- STR, short tandem repeat -- UPD, uniparental disomy -- WCP, whole chromosome painting probe; chromosome 11p15 -- maternal duplication -- Silver-Russell syndrome; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.2004.028936
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Background: Silver-Russell syndrome (SRS) is a heterogeneous malformation syndrome characterised by intrauterine and postnatal growth retardation (IUGR, PGR) and dysmorphisms. The basic causes are unknown, however in approximately 10% of patients a maternal uniparental disomy (UPD) of chromosome 7 or chromosomal aberrations can be detected. Four growth retarded children, two with SRS-like features, associated with maternal duplications of 11p15 have been described. Considering the involvement of this genomic region in Beckwith-Wiedemann overgrowth syndrome (BWS), we postulated that some cases of SRS—with an opposite phenotype to BWS—might also be caused by genomic disturbances in 11p15. Methods: A total of 46 SRS patients were screened for genomic rearrangements in 11p15 by STR typing and FISH analysis. Results: Two SRS patients with duplications of maternal 11p material in our study population (n = 46) were detected. In patient SR46, the duplicated region covered at least 9 Mb; FISH analysis revealed a translocation of 11p15 onto 10q. In patient SR90, additional 11p15 material (approximately 5 Mb) was translocated to the short arm of chromosome 15. Conclusions: We suggest that diagnostic testing for duplication in 11p15 should be offered to patients with severe IUGR and PGR with clinical signs reminiscent of SRS. SRS is a genetically heterogeneous condition and patients with a maternal duplication of 11p15.5 may form an important subgroup.