title: Screening of CYP1B1 and MYOC in Moroccan families with primary congenital glaucoma: three novel mutations in CYP1B1.
abstract: OBJECTIVE
  To investigate the contribution of cytochrome P4501B1 (CYP1B1) and myocillin (MYOC) mutations to primary congenital glaucoma (PCG) in Moroccan families.
  
  
  METHODS
  This study included 90 unrelated families with PCG and 100 normal control individuals. Two previously reported CYP1B1 mutations (g.4339delG and p.G61E) were first screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The coding exons of CYP1B1 were sequenced in g.4339delG- and p.G61E-negative or heterozygous probands. Then the coding exons of MYOC were sequenced in patients who had no mutation in CYP1B1 or carried heterozygous CYP1B1 mutation.
  
  
  RESULTS
  Twelve CYP1B1 mutations were identified in 43 PCG pedigrees. Three of them were novel (p.R163C, p.C470Y, and g.4330-4331delTG) and associated with moderate to severe phenotypes. Two novel intronic polymorphisms in CYP1B1 were identified in addition to those previously described. The g.4339delG was the most frequent mutation detected in 31 families (34.44%), followed by the p.G61E in seven families (7.77%). The remaining mutations (p.R163C, p.E173K, g.4330-4331delTG, p.E229K, p.R390S, p.R368H, p.R469W, p.C470Y, and g.7901-7913del13bp) were infrequent. One family with the p.R390S mutation showed both PCG and primary open angle glaucoma (POAG) phenotypes. One proband was heterozygous for p.T193K mutation in MYOC. This mutation has been initially associated with POAG, but never with PCG.
  
  
  CONCLUSIONS
  Our results support that mutations in CYP1B1 are a major cause for PCG in the Moroccan population with a predominance of the g.4339delG mutation. Furthermore, these results demonstrate the diversity of CYP1B1 mutations, while suggesting a modest role of MYOC in Moroccan PCG.
authors.affiliation: Equipe des Bases Moléculaires de Maladies Génétiques, Université Ibn Tofaïl, Faculté des Sciences, Kénitra, Morocco. lhilal@yahoo.fr
authors.forename: Latifa
authors.initials: L
authors.lastname: Hilal
authors.forename: Soraya
authors.initials: S
authors.lastname: Boutayeb
authors.forename: Aziza
authors.initials: A
authors.lastname: Serrou
authors.forename: Loubna
authors.initials: L
authors.lastname: Refass-Buret
authors.forename: Hafsa
authors.initials: H
authors.lastname: Shisseh
authors.forename: Fatiha
authors.initials: F
authors.lastname: Bencherifa
authors.forename: Mohammed
authors.initials: M
authors.lastname: El Mzibri
authors.forename: Bouchra
authors.initials: B
authors.lastname: Benazzouz
authors.forename: Amina
authors.initials: A
authors.lastname: Berraho
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001189:Aryl Hydrocarbon Hydroxylases / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D065633:Cytochrome P-450 CYP1B1; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D005820:Genetic Testing; D005901:Glaucoma / Q000151:congenital* / Q000201:enzymology / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009018:Morocco; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D016415:Sequence Alignment; D000099179:Myocilin
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D065633:Cytochrome P-450 CYP1B1; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin; C585496:CYP1B1 protein, human