FISH studies in a girl with sporadic aniridia and an apparently balanced de novo t(11;13)(p13;q33) translocation detect a microdeletion involving the WAGR region

Llerena, Juan Clinton; Almeida, João Carlos de Carvalho; Bastos, Elenice Ferreira; Crolla, John A.

doi:10.1590/s1415-47572000000300006

Cited by 2 publications

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“…including deletions, both visible and cryptic (Mannens et al 1991;Fantes et al 1992Fantes et al , 1995aDreschler et al 1994;Kent et al 1997;Crolla et al 1997;Grønskov et al 2001;Muto et al 2002), and inversions, translocations, and insertions (Simola et al 1982;Moore et al 1986;Mannens et al 1991;Fantes et al 1995b;Crolla et al 1996Crolla et al , 1997Llerena et al 2000), have also been reported in association with both isolated sporadic and familial aniridia, as well as in patients with WAGR syndrome. More recently, cell hybrid studies demonstrated inactivation of two independent, aniridia-associated PAX6 alleles, each carrying an ∼1,000-kb submicroscopic deletion distal to PAX6, with the proximal breakpoints at ∼11 kb and ∼22 kb 3 of the PAX6 polyA addition site (Lauderdale et al 2000).…”

Section: Figurementioning

confidence: 99%

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Frequent Chromosome Aberrations Revealed by Molecular Cytogenetic Studies in Patients with Aniridia

Crolla

Heyningen

2002

The American Journal of Human Genetics

133

109

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Seventy-seven patients with aniridia, referred for cytogenetic analysis predominantly to assess Wilms tumor risk, were studied by fluorescence in situ hybridization (FISH), through use of a panel of cosmids encompassing the aniridia-associated PAX6 gene, the Wilms tumor predisposition gene WT1, and flanking markers, in distal chromosome 11p13. Thirty patients were found to be chromosomally abnormal. Cytogenetically visible interstitial deletions involving 11p13 were found in 13 patients, 11 of which included WT1. A further 13 patients had cryptic deletions detectable only by FISH, 3 of which included WT1. Six of these, with deletions <500 kb, share a similar proximal breakpoint within a cosmid containing the last 10 exons of PAX6 and part of the neighboring gene, ELP4. Two of these six patients were mosaic for the deletion. The remaining four had chromosomal rearrangements: an unbalanced translocation, t(11;13), with a deletion including the WAGR (Wilms' tumor, aniridia, genitourinary abnormalities, and mental retardation) region, and three balanced rearrangements with what appear to be position effect breakpoints 3' of PAX6: (a) a t(7;11) with the 11p13 breakpoint approximately 30 kb downstream of PAX6, (b) a dir ins(12;11) with a breakpoint >50 kb from PAX6, and (c) an inv(11)(p13q13) with a breakpoint >75 kb downstream of PAX6. The proportion and spectrum of chromosome anomalies in familial (4/14, or 28.5%) and sporadic (26/63, or 41%) cases are not significantly different. An unexpectedly high frequency of chromosomal rearrangements is associated with both sporadic and familial aniridia in this cohort.

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Section: Figurementioning

confidence: 99%

“…The fourth chromosomal rearrangement, an apparently balanced t(11;13), was found by FISH to have an ∼7.5-Mb deletion at the breakpoint on the der(11) (Llerena et al 2000).…”

Section: Chromosomal Rearrangementsmentioning

confidence: 99%

Frequent Chromosome Aberrations Revealed by Molecular Cytogenetic Studies in Patients with Aniridia

Crolla

Heyningen

2002

The American Journal of Human Genetics

133

109

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A highly complex rea(2;3;11) and aniridia by position effect

Rivera

Ayala-Madrigal

Barros-Núñez

et al. 2006

Cytogenet Genome Res

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A two-year-old boy presenting with bilateral aniridia and psychomotor retardation had a de novo (2;3;11) highly complex rearrangement which was characterized as far as possible by means of G-banding and FISH assays with multiple probes including cosmids for the Wilms, Aniridia, Genital anomalies and Retardation (WAGR) region, alphoid repeats for chromosomes 2, 3 and 11, subtelomere probes for 2p/2q, 3p/3q and 11q and BACs for 2q32 and 3q13. We identified ∼15 breakpoints with at least three interchromosomal and three intrachromosome anomalies involving chromosome 11. Both parents had normal karyotypes and no cryptic 11p rearrangements revealed by the chromosome 11 cosmid panel. The lack of a deletion of PAX6 pointed to the direct insertion of an ∼300-kb segment involving the cosmids FO2121 and AO4160, and more specifically the insertion’s proximal breakpoint in the ∼150-kb segment between FO2121 and FAT5 (PAX6), as the responsible factor for the patient’s aniridia via a position effect resulting in functional haploinsufficiency of the PAX6 gene. This case illustrates the importance of recognizing that de novo complex chromosomal rearrangements found in patients with diverse clinical features may contribute to the phenotype, but that multiple mechanisms and higher levels of complexity may be unmasked by high resolution molecular cytogenetic studies.

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FISH studies in a girl with sporadic aniridia and an apparently balanced de novo t(11;13)(p13;q33) translocation detect a microdeletion involving the WAGR region

Cited by 2 publications

References 15 publications

Frequent Chromosome Aberrations Revealed by Molecular Cytogenetic Studies in Patients with Aniridia

Frequent Chromosome Aberrations Revealed by Molecular Cytogenetic Studies in Patients with Aniridia

A highly complex rea(2;3;11) and aniridia by position effect

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