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.
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 retardedchildren, 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 SRSpatients were screened for genomic rearrangements in 11p15 by STR typing and FISH analysis. RESULTS: Two SRSpatients 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.
Authors: Claire Louise Susan Turner; Deborah M Mackay; Jonathan L A Callaway; Louise E Docherty; Rebecca L Poole; Hilary Bullman; Margaret Lever; Bruce M Castle; Emma C Kivuva; Peter D Turnpenny; Sarju G Mehta; Sahar Mansour; Emma L Wakeling; Verghese Mathew; Jackie Madden; Justin H Davies; I Karen Temple Journal: Eur J Hum Genet Date: 2010-01-27 Impact factor: 4.246
Authors: D J G Mackay; J M D Hahnemann; S E Boonen; S Poerksen; D J Bunyan; H E White; V J Durston; N S Thomas; D O Robinson; J P H Shield; J Clayton-Smith; I K Temple Journal: Hum Genet Date: 2006-01-05 Impact factor: 4.132
Authors: E L Wakeling; S Abu Amero; M Alders; J Bliek; E Forsythe; S Kumar; D H Lim; F MacDonald; D J Mackay; E R Maher; G E Moore; R L Poole; S M Price; T Tangeraas; C L S Turner; M M Van Haelst; C Willoughby; I K Temple; J M Cobben Journal: J Med Genet Date: 2010-08-03 Impact factor: 6.318