Axenfeld-Rieger syndrome (ARS) is associated with ocular and systemic anomalies. PITX2 is known to be a major controlling gene in the pathogenesis of ARS and is associated with differentiation in both the neural crest and mesoderm during eye development. A 4-year-old girl with bilateral ARS had 20 prism diopters (PD) of exotropia with 30PD of A- pattern deviation, more than 20PD of dissociated vertical deviation (DVD), and severe superior oblique overaction (SOOA). During surgery we observed that the SO inserted more posteriorly than normal. We believe this finding is one of the abnormal manifestations of the development of the extraocular muscles in ARS.
*Abnormalities, Multiple ; Anterior Eye Segment/*abnormalities ; Child, Preschool ; Eye Abnormalities/*diagnosis/surgery ; Eye Movements ; Female ; Follow-Up Studies ; Humans ; Oculomotor Muscles/*abnormalities/surgery ; Ophthalmologic Surgical Procedures/*adverse effects ; Optic Nerve/abnormalities ; Postoperative Complications ; Sclera/*pathology/surgery ; Syndrome ; Tooth Abnormalities/*genetics

Axenfeld-Rieger syndrome (ARS) is characterized by anomalies of the anterior segment of the eye and systemic abnormalities. Mutations in the FOXC1 and PITX2 genes are underlying causes of ARS, but there has been few reports on genetically confirmed ARS in Korea. We identified a novel PITX2 mutation (c.300_301delinsT) in 2 Korean patients from a family with ARS. We expand the spectrum of PITX2 mutations and, to the best of our knowledge, this is the first confirmed family of PITX2-related ARS in Korea.
Adult ; Anterior Eye Segment/*abnormalities/pathology ; Base Sequence ; Child, Preschool ; Eye Abnormalities/*genetics/pathology ; Female ; Heterozygote ; Homeodomain Proteins/chemistry/*genetics ; Humans ; Mutation ; Pedigree ; Republic of Korea ; Transcription Factors/chemistry/*genetics

OBJECTIVETo evaluate the role of homozygosity mapping in the fine mapping of the genes responsible for the rare autosomal recessive diseases.

METHODSPolymerase chain reaction-single sequence length polymorphism was used to genotype the family members from 8 families with osteoporosis-pseudoglioma syndrome(OPS) for 14 polymorphic loci within candidate region. The OPS candidate region was narrowed by searching for homozygous region in affected.

RESULTSThe OPS candidate region was narrowed to a 1 cM interval between D11S1296 and D11S4136.

CONCLUSIONHomozygosity mapping is a powerful method for mapping and narrowing the candidate region of the genes responsible for the rare autosomal recessive diseases.

Abnormalities, Multiple ; genetics ; pathology ; Chromosome Mapping ; methods ; Chromosomes, Human, Pair 11 ; genetics ; Eye Diseases ; pathology ; Family Health ; Female ; Genetic Predisposition to Disease ; genetics ; Homozygote ; Humans ; Male ; Microsatellite Repeats ; Osteogenesis Imperfecta ; pathology ; Pedigree ; Syndrome