PMID- 20164457
OWN - NLM
STAT- MEDLINE
DCOM- 20101004
LR  - 20100831
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 51
IP  - 9
DP  - 2010 Sep
TI  - Identification of the IRXB gene cluster as candidate genes in severe dysgenesis 
      of the ocular anterior segment.
PG  - 4380-6
LID - 10.1167/iovs.09-4111 [doi]
AB  - PURPOSE: Anterior segment ocular dysgenesis (ASOD) is a broad heterogeneous group 
      of diseases detectable at the clinical and molecular level. In a patient with 
      bilateral congenital ASOD including aniridia and aphakia, a complex chromosomal 
      rearrangement, inv(2)(p22.3q12.1)t(2;16)(q12.1;q12.2), was characterized at the 
      molecular level, to identify candidate genes implicated in ASOD. METHODS: After 
      negative sequencing of the PAX6, FOXC1, and PITX2 genes, we used fluorescence in 
      situ hybridization (FISH) and Southern blot analysis to characterize the 
      chromosomal breakpoints. Candidate genes were selected, and in situ tissue 
      expression analysis was performed on human fetuses and embryos. RESULTS: 
      Molecular analyses showed that the 16q12.2 breakpoint in this rearrangement 
      occurs in a 625-bp region centromeric to the IRX3 gene, which belongs to the IRXB 
      cluster. In situ hybridization expression studies showed that during early human 
      embryonic development, the IRX3 gene is expressed in the anterior segment of the 
      eye. Of interest, it has been shown previously that a highly conserved noncoding 
      region (HCNCR) is located 300 kb centromeric to the IRX3 gene and induces, in a 
      murine transgenic assay, an expression pattern fitting that of the IRX3 gene. 
      CONCLUSIONS: The authors propose that the 16q12.2 breakpoint of this complex 
      translocation is causally related to the ocular anterior segment dysgenesis 
      observed in this patient. This translocation is assumed to separate the HCNCR 
      from the IRXB cluster genes, thus deregulating the IRXB cluster and leading to 
      the ASOD observed by a positional effect.
FAU - Chaabouni, Myriam
AU  - Chaabouni M
AD  - Service de Cytogenetique, INSERM, Paris, France. chaabouni_myriam@yahoo.fr
FAU - Etchevers, Heather
AU  - Etchevers H
FAU - De Blois, Marie Christine
AU  - De Blois MC
FAU - Calvas, Patrick
AU  - Calvas P
FAU - Waill-Perrier, Marie Christine
AU  - Waill-Perrier MC
FAU - Vekemans, Michel
AU  - Vekemans M
FAU - Romana, Serge Pierrick
AU  - Romana SP
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20100217
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Homeodomain Proteins)
RN  - 0 (IRX3 protein, human)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Anterior Eye Segment/*abnormalities/*physiology
MH  - Chromosome Breakage
MH  - Chromosomes, Human, Pair 16
MH  - Chromosomes, Human, Pair 2
MH  - Eye Abnormalities/*genetics
MH  - Female
MH  - Homeodomain Proteins/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Severity of Illness Index
MH  - Transcription Factors/*genetics
MH  - *Translocation, Genetic
EDAT- 2010/02/19 06:00
MHDA- 2010/10/05 06:00
CRDT- 2010/02/19 06:00
PHST- 2010/02/19 06:00 [entrez]
PHST- 2010/02/19 06:00 [pubmed]
PHST- 2010/10/05 06:00 [medline]
AID - iovs.09-4111 [pii]
AID - 10.1167/iovs.09-4111 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2010 Sep;51(9):4380-6. doi: 10.1167/iovs.09-4111. Epub 
      2010 Feb 17.