Figure 1.
Figure 1. Clinical manifestations of patients carrying VHL mutations and identification of a new VHL spliced isoform containing a cryptic exon. (A) Mutations in the VHL gene predispose to different phenotypes. VHL disease is characterized by the development of central nervous system (CNS) and retinal hemangioblastomas, neuroendocrine pancreatic tumors, pheochromocytomas, and clear cell renal cell carcinomas. Chuvash polycythemia (erythrocytosis) is characterized by elevated red blood cell numbers. This study describes families with typical VHL-related phenotypes associated with an unexpected VHL status (ie, either synonymous mutations or no alterations in VHL). (B) Reverse transcription polymerase chain reaction (RT-PCR) using primers specific for E1 and E3 was performed on messenger RNA (mRNA) extracted from lymphoblastoid cell lines (LCLs) established from controls and patients of family 1 (F1). (C) Schematic representation of the VHL gene and its products. The different VHL exons are represented on a scale: E1, 340 bp from the ATG initiation codon; E1′, 259 bp; E2, 123 bp; E3, 179 bp to the Stop termination codon. The full-length VHL mRNA isoform encodes pVHL213 (also named pVHL30). VHL E1 contains an internal translation initiation codon that initiates the production of pVHL160 protein (pVHL19). The isoform containing E1 spliced in phase with E3 encodes pVHL172 that lacks E2. The isoforms containing E1 spliced with E1′ may theoretically encode a protein termed X1 of 193 aa (114 aa encoded by E1, and 79 aa encoded by E1′). Consensus values of donor (SD) and acceptor (SA) splice site sequences are indicated above the VHL gene, as calculated by the human splicing finder in silico tool. Horizontal blue lines indicate the location of probes used in TaqMan assays. *Denotes larger fragments that were subsequently cloned and sequenced. †The isoforms containing E1′ spliced with VHL exons were identified by cloning and sequencing in the laboratory but were described later by the National Center for Biotechnology Information as transcripts able to produce a protein termed X1. WT, wild type.

Clinical manifestations of patients carrying VHL mutations and identification of a new VHL spliced isoform containing a cryptic exon. (A) Mutations in the VHL gene predispose to different phenotypes. VHL disease is characterized by the development of central nervous system (CNS) and retinal hemangioblastomas, neuroendocrine pancreatic tumors, pheochromocytomas, and clear cell renal cell carcinomas. Chuvash polycythemia (erythrocytosis) is characterized by elevated red blood cell numbers. This study describes families with typical VHL-related phenotypes associated with an unexpected VHL status (ie, either synonymous mutations or no alterations in VHL). (B) Reverse transcription polymerase chain reaction (RT-PCR) using primers specific for E1 and E3 was performed on messenger RNA (mRNA) extracted from lymphoblastoid cell lines (LCLs) established from controls and patients of family 1 (F1). (C) Schematic representation of the VHL gene and its products. The different VHL exons are represented on a scale: E1, 340 bp from the ATG initiation codon; E1′, 259 bp; E2, 123 bp; E3, 179 bp to the Stop termination codon. The full-length VHL mRNA isoform encodes pVHL213 (also named pVHL30). VHL E1 contains an internal translation initiation codon that initiates the production of pVHL160 protein (pVHL19). The isoform containing E1 spliced in phase with E3 encodes pVHL172 that lacks E2. The isoforms containing E1 spliced with E1′ may theoretically encode a protein termed X1 of 193 aa (114 aa encoded by E1, and 79 aa encoded by E1′). Consensus values of donor (SD) and acceptor (SA) splice site sequences are indicated above the VHL gene, as calculated by the human splicing finder in silico tool. Horizontal blue lines indicate the location of probes used in TaqMan assays. *Denotes larger fragments that were subsequently cloned and sequenced. †The isoforms containing E1′ spliced with VHL exons were identified by cloning and sequencing in the laboratory but were described later by the National Center for Biotechnology Information as transcripts able to produce a protein termed X1. WT, wild type.

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal