Novel mutations of FOXC1 and PITX2 in patients with Axenfeld-Rieger malformations
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Novel mutations of FOXC1 and PITX2 in patients with Axenfeld-Rieger malformations. / Weisschuh, Nicole; Dressler, Paul; Schuettauf, Frank; Wolf, Christiane; Wissinger, Bernd; Gramer, Eugen.
In: INVEST OPHTH VIS SCI, Vol. 47, No. 9, 09.2006, p. 3846-52.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Novel mutations of FOXC1 and PITX2 in patients with Axenfeld-Rieger malformations
AU - Weisschuh, Nicole
AU - Dressler, Paul
AU - Schuettauf, Frank
AU - Wolf, Christiane
AU - Wissinger, Bernd
AU - Gramer, Eugen
PY - 2006/9
Y1 - 2006/9
N2 - PURPOSE: To determine the prevalence of FOXC1 and PITX2 mutations and to assess clinical phenotypes in a cohort of German patients with Axenfeld-Rieger malformations.METHODS: All coding exons of the FOXC1 and PITX2 genes were amplified by PCR from genomic DNA and subjected to direct DNA sequencing. Analysis of mutations in control subjects was performed by restriction fragment length polymorphism (RFLP) analysis.RESULTS: Sequence variants were identified by DNA sequencing in 15 of 19 cases. Mutation screening identified four potentially pathogenic FOXC1 mutations causing amino acid substitutions (P79R, Y115S, G149D, and M161V) that were not present in 100 control subjects. In addition, two different 1-bp deletions causing a frameshift and subsequent premature stop codon were identified in two subjects. One patient harbored a FOXC1 nonsense mutation (S48X). Mutation screening also identified two potentially pathogenic PITX2 mutations (P64L and P64R) in two index patients that were excluded in 100 healthy control subjects.CONCLUSIONS: The findings in the present study clearly demonstrate that FOXC1 and PITX2 mutations are responsible for a significant proportion of Axenfeld-Rieger malformations in Germany.
AB - PURPOSE: To determine the prevalence of FOXC1 and PITX2 mutations and to assess clinical phenotypes in a cohort of German patients with Axenfeld-Rieger malformations.METHODS: All coding exons of the FOXC1 and PITX2 genes were amplified by PCR from genomic DNA and subjected to direct DNA sequencing. Analysis of mutations in control subjects was performed by restriction fragment length polymorphism (RFLP) analysis.RESULTS: Sequence variants were identified by DNA sequencing in 15 of 19 cases. Mutation screening identified four potentially pathogenic FOXC1 mutations causing amino acid substitutions (P79R, Y115S, G149D, and M161V) that were not present in 100 control subjects. In addition, two different 1-bp deletions causing a frameshift and subsequent premature stop codon were identified in two subjects. One patient harbored a FOXC1 nonsense mutation (S48X). Mutation screening also identified two potentially pathogenic PITX2 mutations (P64L and P64R) in two index patients that were excluded in 100 healthy control subjects.CONCLUSIONS: The findings in the present study clearly demonstrate that FOXC1 and PITX2 mutations are responsible for a significant proportion of Axenfeld-Rieger malformations in Germany.
KW - Amino Acid Sequence
KW - Anterior Eye Segment/abnormalities
KW - Codon/genetics
KW - DNA Mutational Analysis
KW - Eye Abnormalities/genetics
KW - Female
KW - Forkhead Transcription Factors/genetics
KW - Glaucoma/genetics
KW - Homeodomain Proteins/genetics
KW - Humans
KW - Intraocular Pressure/genetics
KW - Iris/abnormalities
KW - Male
KW - Molecular Sequence Data
KW - Mutation
KW - Pedigree
KW - Polymerase Chain Reaction
KW - Polymorphism, Restriction Fragment Length
KW - Sequence Analysis, DNA
KW - Transcription Factors/genetics
U2 - 10.1167/iovs.06-0343
DO - 10.1167/iovs.06-0343
M3 - SCORING: Journal article
C2 - 16936096
VL - 47
SP - 3846
EP - 3852
JO - INVEST OPHTH VIS SCI
JF - INVEST OPHTH VIS SCI
SN - 0146-0404
IS - 9
ER -
