Fusion of a novel gene, RCC17, to the TFE3 gene in t(X;17)(p11.2;q25.3)-bearing papillary renal cell carcinomas.

A subset of childhood and young adult renal cell carcinomas displays a recurrent translocation t(X;17)(p11;q25) as the sole cytogenetic abnormality. In two young girls, we demonstrate that this translocation results in the fusion of a novel gene, designated RCC17, at chromosome 17q25, to the transcription factor TFE3 located on the Xp11 chromosomal region. In both cases, the t(X;17) fuses the NH(2)-terminal region of RCC17 to the COOH-terminal part of TFE3 including the basic helix-loop-helix DNA-binding domain and the leucine zipper dimerization domain. The reciprocal fusion transcript TFE3/RCC17 is also expressed. RCC17 encodes a putative protein of 553 amino acids. It is ubiquitously expressed in normal adult tissues. No significant similarity was found with other fusion partners of TFE3 or with any relevant functional protein domains, precluding informed speculation about the normal function of this gene.Case ReportsJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Copy number variation upstream of PMP22 in Charcot–Marie–Tooth disease

In several individuals with a Charcot–Marie–Tooth (CMT) phenotype, we found a copy number variation (CNV) on chromosome 17p12 in the direct vicinity of the peripheral myelin protein 22 (PMP22) gene. The exact borders and size of this CNV were determined by Southern blot analysis, MLPA, vectorette PCR, and microarray hybridization analyses. All patients from six apparently unrelated families carried an identical 186-kb duplication different from the commonly reported 1.5-Mb duplication associated with CMT1A. This ancestral mutation that was not reported in the human structural variation database was only detected in affected individuals and family members. It was absent in 2124 control chromosomes and 40 patients with a chronic inflammatory demyelinating polyneuropathy (CIDP) and therefore should be regarded as causative for the disease. This variant escapes most routine diagnostic screens for CMT1A, because copy numbers of PMP22 probes were all normal. No indications were found for the involvement of the genes that are located within this duplication. A possible association of this duplication with a mutation in the PMP22 coding regions was also excluded. We suggest that this CNV proximal of the PMP22 gene leads to CMT through an unknown mechanism affecting PMP22 expression