Purpose: To provide genetic counseling and presymptomatic diagnosis to family members by investigating the genetic cause of a large primary juvenile open angle glaucoma (JOAG) pedigree with an autosomal dominant pattern.
Methods: Ocular examinations were performed on all members of the pedigree in order to determine their disease status. Subjects were labeled as affected individuals, unaffected individuals, and suspects. Genomic DNA was extracted from the peripheral blood of the family members. Three exons of MYOC, 12 coding exons of OPTN, and two coding exons of CYP1B1 were amplified by polymerase chain reaction (PCR). Direct DNA sequencing was used to identify mutations in MYOC, OPTN, and CYP1B1. Presymptomatic diagnoses were made for the consulters based on the results of both clinical examination and genetic analysis.
Results: One heterozygous mutation in the MYOC gene was identified in all patients of the pedigree. It was a cytosine to thymine transition at nucleotide 1,109, which corresponded to an amino acid residue change from proline to leucine at codon 370. The Pro370Leu mutation correlated with a severe JOAG phenotype as previously reported. Two adolescents, who were labeled as suspects, were detected to carry the same mutation and thus had a high risk of developing glaucoma. Close follow-up at regular intervals was recommended. In addition, no pathogenic mutations of OPTN and CYP1B1 were detected.
Conclusions: The Pro370Leu mutation of the MYOC gene contributed to JOAG in this pedigree. Early onset, rapid development, poor response to medicine and high penetrance are characteristics of this mutation. Genetic analysis is valuable for providing genetic counseling and presymptomatic diagnosis to members in typical autosomal inheritance pedigrees with JOAG.