Phenotypic variability and asymmetry of Rieger syndrome associated with PITX2 mutations.
Invest Ophthalmol Vis Sci
; 41(9): 2456-60, 2000 Aug.
Article
in En
| MEDLINE
| ID: mdl-10937553
ABSTRACT
PURPOSE:
Rieger syndrome is an autosomal dominant condition characterized by a variable combination of anterior segment dysgenesis, dental anomalies, and umbilical hernia. To date, reports have shown mutations within the PITX2 gene associated with Rieger syndrome, iridogoniodysgenesis, and iris hypoplasia. The purposes of this study were to determine the range of expression and intrafamilial variability of PITX2 mutations in patients with anterior segment dysgenesis.METHODS:
Seventy-six patients with different forms of anterior segment dysgenesis were classified clinically. DNA was obtained and screened by means of polymerase chain reaction (PCR)-single-stranded conformation polymorphism (SSCP) and heteroduplex analysis followed by direct sequencing.RESULTS:
Eight of 76 patients had mutations within the PITX2 gene. Anterior segment phenotypes show wide variability and include a phenocopy of aniridia and Peters', Rieger, and Axenfeld anomalies. Mutations include premature terminations and splice-site and homeobox mutations, confirming that haploinsufficiency the likely pathogenic mechanism in the majority of cases.CONCLUSIONS:
There is significant phenotypic variability in patients with PITX2 mutations, both within and between families. Developmental glaucoma is common. The umbilical and dental abnormalities are highly penetrant, define those at risk of carrying mutations in this gene, and guide mutation analysis. In addition, there is a range of other extraocular manifestations.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Uveal Diseases
/
Nuclear Proteins
/
Eye Diseases, Hereditary
/
Iris
/
Homeodomain Proteins
/
Eye Proteins
/
Mutation
Type of study:
Risk_factors_studies
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Invest Ophthalmol Vis Sci
Year:
2000
Document type:
Article
Affiliation country:
Reino Unido