A novel mutation in the PITX2 gene in a family with Axenfeld-Rieger syndrome. Ophthalmic Genet 2004 Mar;25(1):57-62
Date
07/17/2004Pubmed ID
15255117DOI
10.1076/opge.25.1.57.29002Scopus ID
2-s2.0-1942422639 (requires institutional sign-in at Scopus site) 26 CitationsAbstract
PURPOSE: To determine the underlying genetic cause of Axenfeld-Rieger syndrome (ARS) in a three-generation family.
INTRODUCTION: ARS is a multisystem, autosomal dominant disorder characterized by specific ocular and non-ocular anomalies sometimes caused by mutations in the transcription factor gene, PITX2.
METHODS: The three coding exons of the PITX2 gene, i.e., exons 2, 3, and 4, in affected and unaffected subjects were amplified by polymerase chain reaction (PCR) and sequenced. The PCR products of exon 4 were subcloned and sequenced to confirm the nature of the mutation.
RESULTS: A deletion of thymine (T) 1261 was identified, creating a frameshift mutation in codon 227. This change is predicted to create 11 novel amino acids downstream, followed by premature truncation of the protein.
CONCLUSIONS: This mutation highlights the functional importance of a conserved 14-amino acid sequence at the C-terminus of the protein thought to be important in repressing DNA binding and in protein-protein interactions.
Author List
Brooks BP, Moroi SE, Downs CA, Wiltse S, Othman MI, Semina EV, Richards JEAuthor
Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Abnormalities, MultipleAdult
Anodontia
Anterior Eye Segment
DNA Mutational Analysis
Exons
Female
Frameshift Mutation
Glaucoma
Homeodomain Proteins
Humans
Iris
Middle Aged
Myopia
Pedigree
Polymerase Chain Reaction
Syndrome
Transcription Factors
