Combination of WAGR and Potocki-Shaffer contigous deletion syndromes in a patient with an 11p11.2-p14 deletion

Department of Ophthalmology, Robert Debré Hospital, AP-HP, Paris, France.
European Journal of HumanGenetics (Impact Factor: 4.35). 05/2005; 13(4):409-13. DOI: 10.1038/sj.ejhg.5201358
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Aniridia, Wilms tumor, genitourinary abnormalities, growth and mental retardation are the cardinal features of the WAGR 11p13 deletion syndrome. The Potocki-Schaffer syndrome or proximal 11p deletion syndrome (previously DEFECT11 syndrome) is a contiguous gene syndrome associated with deletions in 11p11.2, principal features of which are multiple exostoses and enlarged parietal foramina. Mental handicap, facial dysmorphism and craniosynostosis may also be associated. We report a patient with combined WAGR and Potocki-Shaffer syndromes, and obesity. She presented with aniridia, cataract, nystagmus, corneal ulcers and bilateral congenital ptosis. A left nephroblastoma was detected at 15 months. Other features included moderate developmental delay, growth deficiency, facial dysmorphism, multiple exostoses and cranial lacunae. High-resolution and molecular cytogenetics confirmed a del(11)(p11.2p14.1) deletion with a proximal breakpoint between the cosmid DO8153 and the BAC RP11-104M24 to a distal breakpoint between cosmids CO8160 (D11S151) and F1238 (D11S1446). The deletion therefore includes EXT2, ALX4, WT1 and PAX6. This case appears to be the second patient reported with this combined deletion syndrome and confirms the association of obesity in the WAGR spectrum, a feature previously reported in four cases, and for which the acronym WAGRO has been suggested. Molecular and follow-up data on the original WAGRO case are briefly presented.

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Available from: Dominique Bremond-Gignac, Mar 04, 2014
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    • "However, the genotype-phenotype correlation was clear enough for the diagnosis of PSS. So far, 46 patients from 31 families affected by PSS have been described [Francke et al., 1977; Gustavson et al., 1984; Lorenz et al., 1990; Shaffer et al., 1993; McGaughran et al., 1995; Bartsch et al., 1996; Potocki and Shaffer, 1996; Wuyts et al., 1999, 2004; Hall et al., 2001; Yamamoto et al., 2001; Chien et al., 2003; Brémond-Gignac et al., 2005; Chuang et al., 2005; Wakui et al., 2005; Romeike and Wuyts, 2007; Almind et al., 2009; Swarr et al., 2010]. The clinical phenotype of PSS is extremely heterogeneous, from normal development and intelligence to severe developmental delay and other abnormalities, including WAGR syndrome, due to the size of the deletion. "
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    ABSTRACT: We describe the case of an adult patient affected by multiple exostoses, severe mental retardation, epilepsy and facial dysmorphisms with a deletion of ∼2.3 Mb on chromosome 11p11.21, correlated to Potocki-Shaffer syndrome (PSS). PSS is a rare contiguous gene deletion syndrome, mainly characterized by multiple exostoses and bilateral parietal foramina. Mental retardation and craniofacial dysmorphisms have often been reported, too. Although the patient showed many signs of PSS since early childhood, the diagnosis was suggested only when we examined her at adult age. This case highlights how frequently rare diseases remain undiagnosed till adulthood and is an excellent example of the need for a timely and correct diagnosis.
    Molecular syndromology 04/2012; 2(6):259-261. DOI:10.1159/000337925
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    • "This patient exhibited features of both WAGR as well as PSS; developmental delay but no seizures. Bremond-Gignac et al described a further case with 11p deletion encompassing EXT2, ALX4, WT1 and PAX6 genes showing features of both WAGR and PSS [15]. In addition, the patient showed obesity. "
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    ABSTRACT: WAGR syndrome (Wilms' tumor, aniridia, genitourinary abnormalities and mental retardation) and Potocki-Shaffer syndrome are rare contiguous gene deletion syndromes caused by deletions of the 11p14-p12 chromosome region. We present a patient with mental retardation, unilateral cataract, bilateral ptosis, genital abnormalities, seizures and a dysmorphic face. Cytogenetic analysis showed a deletion on 11p that was further characterized using FISH and MLPA analyses. The deletion (11p13-p12) located in the area between the deletions associated with the WAGR and Potocki-Shaffer syndromes had a maximum size of 8.5 Mb and encompasses 44 genes. Deletion of WT1 explains the genital abnormalities observed. As PAX6 was intact the cataract observed cannot be explained by a deletion of this gene. Seizures have been described in Potocki-Shaffer syndrome while mental retardation has been described in both WAGR and Potocki-Shaffer syndrome. Characterization of this patient contributes further to elucidate the function of the genes in the 11p14-p12 chromosome region.
    Molecular Cytogenetics 03/2009; 2(1):6. DOI:10.1186/1755-8166-2-6 · 2.14 Impact Factor
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    ABSTRACT: This report constitutes the seventh update of the human obesity gene map incorporating published results up to the end of October 2000. Evidence from the rodent and human obesity cases caused by single-gene mutations, Mendelian disorders exhibiting obesity as a clinical feature, quantitative trait loci uncovered in human genome-wide scans and in cross-breeding experiments in various animal models, and association and linkage studies with candidate genes and other markers are reviewed. Forty-seven human cases of obesity caused by single-gene mutations in six different genes have been reported in the literature to date. Twenty-four Mendelian disorders exhibiting obesity as one of their clinical manifestations have now been mapped. The number of different quantitative trait loci reported from animal models currently reaches 115. Attempts to relate DNA sequence variation in specific genes to obesity phenotypes continue to grow, with 130 studies reporting positive associations with 48 candidate genes. Finally, 59 loci have been linked to obesity indicators in genomic scans and other linkage study designs. The obesity gene map reveals that putative loci affecting obesity-related phenotypes can be found on all chromosomes except chromosome Y. A total of 54 new loci have been added to the map in the past 12 months and the number of genes, markers, and chromosomal regions that have been associated or linked with human obesity phenotypes is now above 250. Likewise, the number of negative studies, which are only partially reviewed here, is also on the rise.
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