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Bilateral multiple renal oncocytomas and cysts associated with a constitutional translocation (8;9)(q24.1;q34.3) and a rare constitutional VHL missense substitution

✍ Scribed by Bin T. Teh; Elizabeth Blennow; Sophie Giraud S; Sigrid Sahlén; Su I. Hii; Ross Brookwell; Hiltrud Brauch; Magnus Nordenskjöld; Catharina Larsson; David Nicol


Publisher
John Wiley and Sons
Year
1998
Tongue
English
Weight
493 KB
Volume
21
Category
Article
ISSN
1045-2257

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✦ Synopsis


We report here on a patient with bilateral multifocal renal oncocytomas and cysts. Cytogenetic analysis of the patient's lymphocytes revealed a constitutional 46,XY,add (9)(q34.3) karyotype. The rearrangement was further resolved as a constitutional reciprocal t(8;9)(q24.1;q34.3) by microdissection and FISH. Because the 9q breakpoint was located in the same region as the tuberous sclerosis type 1 locus (TSC1), which is associated with renal tumors, we performed FISH with two TSC1 flanking cosmids that were mapped proximal to the 9q breakpoint, thus excluding its involvement. Loss of heterozygosity (LOH) studies of the tumors revealed LOH in chromosome 1, further strengthening the molecular diagnosis of oncocytoma. A previously unreported germline missense substitution, Pro40Arg, in exon 1 of the VHL gene was also found in the patient's constitutional DNA, adding to the complexity of the genetic profile.