Molecular genetic analysis of a de novo balanced translocation t(6;17)(p21.31;qll.2) associated with hypospadias and anorectal malformation

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 par...

Full description

Saved in:

Bibliographic Details
Published in:	Human genetics Vol. 119; no. 1-2; pp. 162 - 168
Main Authors:	MANSOURI, Mahmoud Reza, CARLSSON, Birgit, DAVEY, Edward, NORDENSKJÖLD, Agneta, WESTER, Tomas, ANNEREN, Göran, LÄCKGREN, Cöran, DAHL, Niklas
Format:	Journal Article
Language:	English
Published:	Heidelberg Springer 01-03-2006 Berlin Springer Nature B.V New York, NY
Subjects:	Abnormalities, Multiple - genetics Abnormalities, Multiple - pathology Anal Canal - abnormalities Base Sequence Biological and medical sciences Child Chromosome Breakage Chromosomes, Human, Pair 17 Chromosomes, Human, Pair 6 Classical genetics, quantitative genetics, hybrids Female Fundamental and applied biological sciences. Psychology Gene Expression Profiling Genetics of eukaryotes. Biological and molecular evolution Human Humans Hypospadias - pathology Male Malformations of the urinary system Medical sciences Medicin och hälsovetenskap Mutant Chimeric Proteins - genetics Nephrology. Urinary tract diseases Rectum - abnormalities Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Messenger - metabolism Translocation, Genetic - genetics Urinary system involvement in other diseases. Miscellaneous Urinary tract. Prostate gland Translocation Urinary system disease Urethral disease Malformation Hypospadias CDKN1A Gene Genetics Anorectal Urinary tract disease Genetic determinism De novo
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
Bibliography:	ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3
ISSN:	0340-6717 1432-1203 1432-1203
DOI:	10.1007/s00439-005-0122-9