Presymptomatic genetic diagnosis for consulters from a largeChinese family with juvenile open angle glaucoma

[摘要] Purpose: To provide genetic counseling and presymptomatic diagnosisto family members by investigating the genetic cause of a large primaryjuvenile open angle glaucoma (JOAG) pedigree with an autosomal dominantpattern.Methods: Ocular examinations were performed on all members of thepedigree in order to determine their disease status. Subjects werelabeled as affected individuals, unaffected individuals, and suspects.Genomic DNA was extracted from the peripheral blood of the familymembers. Three exons of MYOC, 12 coding exons of OPTN, and twocoding 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 theconsulters based on the results of both clinical examination and geneticanalysis.Results: One heterozygous mutation in the MYOC gene wasidentified in all patients of the pedigree. It was a cytosine to thyminetransition at nucleotide 1,109, which corresponded to an amino acidresidue change from proline to leucine at codon 370. The Pro370Leumutation correlated with a severe JOAG phenotype as previously reported.Two adolescents, who were labeled as suspects, were detected to carrythe same mutation and thus had a high risk of developing glaucoma. Closefollow-up at regular intervals was recommended. In addition, nopathogenic mutations of OPTN and CYP1B1 were detected.Conclusions: The Pro370Leu mutation of the MYOC gene contributedto JOAG in this pedigree. Early onset, rapid development, poor responseto medicine and high penetrance are characteristics of this mutation.Genetic analysis is valuable for providing genetic counseling andpresymptomatic diagnosis to members in typical autosomal inheritancepedigrees with JOAG.

[学科分类] 生物化学/生物物理