PERICENTRIC INTRACHROMOSOMAL INSERTION RESPONSIBLE FOR RECURRENCE OF DEL(11)(P13P14) IN A FAMILY

The combined use of qualitative and quantitative analysis of 11p13 pol ymorphic markers together with chromosomal in situ suppression hybridi zation (CISS) with biotin labeled probes mapping to 11p allowed us to characterize a complex rearrangement segregating in a family. We detec ted a pericentric intrachromosomal insertion responsible for recurrenc e of del(11)(p13p14) in the family: an insertion of band 11p13-p14 car rying the genes for predisposition to Wilms' tumor, VT1, and for aniri dia, AN2, into the long arm of chromosome 11 in 11q13-q14. Asymptomati c balanced carriers were observed over three generations. Classical cy togenetics had failed to detect this anomaly in the balanced carriers, who were first considered to be somatic mosaics for del(11)(p13). Two of these women gave birth to children carrying a deleted chromosome 1 1, most likely resulting from the loss of the 11p13 band inserted in 1 1q. Although in both cases the deletion encompassed exactly the same m aternally inherited markers, there was a wide variation in clinical ex pression. One child, with the karyotype 46,XY,del(11)(p13p14), present ed the full-blown WAGR syndrome with aniridia, mental retardation, Wil ms' tumor, and pseudohermaphroditism, but also had proteinuria and glo merular sclerosis reminiscent of Drash syndrome. In contrast, the othe r one, a girl with the karyotype 46,XX,del(11)(p13), only had aniridia . Although a specific set of mutational sites has been observed in Dra sh patients, these findings suggest that the loss of one copy of the W T1 gene can result in similar genital and kidney abnormalities.