PURPOSE: To establish the genotype-phenotype correlations of various CYP1B1 (human cytochrome P450) mutations in patients in India with primary congenital glaucoma (PCG). METHODS: The study cohort comprised 146 patients with PCG from 138 pedigrees. Patients were analyzed for six distinct CYP1B1 mutations by sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. A severity index for grading various PCG phenotypes was constructed based on clinical parameters. RESULTS: Six mutations were identified in 45 patients analyzed and genotype-phenotype correlations were established for 43 of them. The percentages of severe phenotypes associated with various mutations in at least one eye were: frameshift, 100%; G61E, 66.7%; P193L, 62.5%; E229K, 80%; R368H, 72%; R390C, 83.3%. The frameshift mutation resulted in blindness. Based on the severity index, the disease severity was graded from normal to severe and the prognosis from good to very poor (blind). De novo mutation was identified in one family. CONCLUSIONS: This is the first study to attempt to devise a severity index for grading various PCG phenotypes and to use genotype as an indicator to predict the prognoses of the disorder. This index may help guide therapy and counseling of the afflicted family regarding the progression of the disorder. All patients with severe phenotypes showed poor prognoses (r = 0.976; P < 0.0001). The data derived from this study could be used as an added clinical tool in disease management. Integrated management of PCG that makes use of a genetic approach could yield better results than medical, surgical, and rehabilitation interventions alone.
PURPOSE: To establish the genotype-phenotype correlations of various CYP1B1 (human cytochrome P450) mutations in patients in India with primary congenital glaucoma (PCG). METHODS: The study cohort comprised 146 patients with PCG from 138 pedigrees. Patients were analyzed for six distinct CYP1B1 mutations by sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. A severity index for grading various PCG phenotypes was constructed based on clinical parameters. RESULTS: Six mutations were identified in 45 patients analyzed and genotype-phenotype correlations were established for 43 of them. The percentages of severe phenotypes associated with various mutations in at least one eye were: frameshift, 100%; G61E, 66.7%; P193L, 62.5%; E229K, 80%; R368H, 72%; R390C, 83.3%. The frameshift mutation resulted in blindness. Based on the severity index, the disease severity was graded from normal to severe and the prognosis from good to very poor (blind). De novo mutation was identified in one family. CONCLUSIONS: This is the first study to attempt to devise a severity index for grading various PCG phenotypes and to use genotype as an indicator to predict the prognoses of the disorder. This index may help guide therapy and counseling of the afflicted family regarding the progression of the disorder. All patients with severe phenotypes showed poor prognoses (r = 0.976; P < 0.0001). The data derived from this study could be used as an added clinical tool in disease management. Integrated management of PCG that makes use of a genetic approach could yield better results than medical, surgical, and rehabilitation interventions alone.
Authors: Fereshteh Chitsazian; Betsabeh Khoramian Tusi; Elahe Elahi; Heidar Amini Saroei; Mohammad H Sanati; Shahin Yazdani; Mohammad Pakravan; Navid Nilforooshan; Yadollah Eslami; Mohammad Ali Zare Mehrjerdi; Reza Zareei; Mahmood Jabbarvand; Ali Abdolahi; Ali R Lasheyee; Arash Etemadi; Behnaz Bayat; Mehdi Sadeghi; Mohammad M Banoei; Behnam Ghafarzadeh; Mohammad R Rohani; Akram Rismanchian; Yvonne Thorstenson; Mansoor Sarfarazi Journal: J Mol Diagn Date: 2007-07 Impact factor: 5.568
Authors: Malkaram S Achary; Aramati B M Reddy; Subhabrata Chakrabarti; Shirly G Panicker; Anil K Mandal; Niyaz Ahmed; Dorairajan Balasubramanian; Seyed E Hasnain; Hampapathalu A Nagarajaram Journal: Biophys J Date: 2006-09-08 Impact factor: 4.033
Authors: David A Hollander; Mansoor Sarfarazi; Ivaylo Stoilov; Irmgard S Wood; Douglas R Fredrick; Jorge A Alvarado Journal: Trans Am Ophthalmol Soc Date: 2006