We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Molecular genetic analysis of a de novo balanced translocation t(6;17)(p21.31;q11.2) associated with hypospadias and anorectal malformation.
- Authors
Mansouri, Mahmoud; Carlsson, Birgit; Davey, Edward; Nordenskjöld, Agneta; Wester, Tomas; Annerén, Göran; Läckgren, Göran; Dahl, Niklas
- Abstract
We report a young boy with penoscrotal hypospadias, anal atresia (AA) with a recto-urethral fistula, a hypoplastic kidney and a balanced translocation t(6;17)(p21.31;q11.2). Physical mapping of the breakpoints localized the chromosome 6 breakpoint within an intron of the gene lipoma HMGIC fusion partner-like 5 ( LHFPL5) whereas the chromosome 17 breakpoint was mapped to the first intron of the 182-FIP gene encoding the Fragile X Mental Retardation Protein Interacting Protein. Sequence analysis across the breakpoints revealed an almost perfectly balanced translocation with a 2 bp deletion on the derivative chromosome 6 and a 7 bp duplication on the derivative chromosome 17. We identified a fusion transcript consisting of the first exon of 182-FIP and the last exon of LHFPL5 in patient-derived cells. Quantitative expression analysis of the genes flanking the breakpoints, revealed increased transcript levels for SFRS protein kinase 1 ( SRPK1) and TAO kinase 1 ( TAOK1) which suggests a positional effect due to the translocation. We hypothesize that the urogenital and anorectal malformations in the patient result from one or several mechanisms including disruption of the genes 182-FIP and LHFPL5, altered expression of the genes flanking the translocation breakpoints and, a gain of function mechanism mediated by the 182-FIP-LHFPL5 fusion transcript.
- Subjects
HYPOSPADIAS; PENIS abnormalities; BILIARY atresia; INTELLECTUAL disabilities; DEVELOPMENTAL disabilities; DNA-protein interactions; GENETIC mutation
- Publication
Human Genetics, 2006, Vol 119, Issue 1/2, p162
- ISSN
0340-6717
- Publication type
Article
- DOI
10.1007/s00439-005-0122-9