A novel mutation in the PITX2 gene in a family with Axenfeld-Rieger syndrome.
OBJECTIVE
To determine the underlying genetic cause of Axenfeld-Rieger syndrome (ARS) in a three-generation family.


BACKGROUND
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.
Brooks
Brian P
BP
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA. brooksb@mail.nih.gov
Moroi
Sayoko E
SE
Downs
Catherine A
CA
Wiltse
Shannon
S
Othman
Mohammad I
MI
Semina
Elena V
EV
Richards
Julia E
JE
D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D000848:Anodontia / Q000235:genetics; D000869:Anterior Eye Segment / Q000002:abnormalities*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D005901:Glaucoma / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007498:Iris / Q000002:abnormalities*; D008875:Middle Aged; D009216:Myopia / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D000097577:Homeobox Protein PITX2
D018398:Homeodomain Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2