title: Clinical Variability of Primary Congenital Glaucoma in a Spanish Family With Cyp1b1 Gene Mutations.
abstract: BACKGROUND
  Primary congenital glaucoma (PCG) is a rare disease. In around a third of Spanish patients, the disease is attributed to mutations in the CYP1B1 gene inherited in an autosomal recessive manner. Such mutations are the main known genetic cause of PCG.
  
  
  METHODS
  We describe the case of a family with 3 of 7 siblings diagnosed with PCG. In a genetic study of the CYP1B1 gene, 2 null mutations were identified in the affected siblings (R355fsX69/T404fsX38). Two of the 4 healthy siblings were heterozygous for mutation R355fsX69 and the remaining 2 had no mutations. The healthy parents were found to be heterozygous for mutations T404fsX38 (mother) and R355fsX69 (father). High variation in the expression of PCG was observed, especially in terms of disease onset and severity: Patient 1 in the eldest affected sibling, PCG was diagnosed at 8 years of age and is presently stable after 60 months of medical treatment; patient 2 the second affected child underwent surgery at 7 days of age. Today, at 104 months, she has undergone 2 operations on the right eye and 3 on the left eye; patient 3 the youngest sibling, the disease also manifested at birth and the boy underwent surgery at 4 days. Currently he is 84 months old, he has required 7 operations for glaucoma, 3 in the right eye and 4 in the left.
  
  
  CONCLUSIONS
  This clinical case reveals the etiological relationship between CYP1B1 mutations and PCG. In addition, it indicates a highly variable clinical picture associated with a single disease genotype mainly affecting disease onset and progression.
authors.affiliation: *Servicio de Oftalmologia, Hospital Clinico San Carlos, Instituto de Investigacion Sanitaria del Hospital Clinico San Carlos (IdISSC) †Departamento de Oftalmologia y ORL, Facultad de Medicina, Universidad Complutense de Madrid ‡Instituto de Investigaciones Oftalmologicas Ramon Castroviejo, Universidad Complutense de Madrid ∥Cooperative Research Network on Age-Related Ocular Pathology, Visual and Life Quality, Instituto de Salud Carlos III, Madrid §Área de Genética, Facultad de Medicina/Instituto de Investigación en Discapacidades Neurlógicas (IDINE), Universidad de Castilla-La Mancha, Albacete, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Morales-Fernandez
authors.forename: Jose M
authors.initials: JM
authors.lastname: Martinez-de-la-Casa
authors.forename: Javier
authors.initials: J
authors.lastname: Garcia-Bella
authors.forename: Carmen
authors.initials: C
authors.lastname: Mendez
authors.forename: Federico
authors.initials: F
authors.lastname: Saenz-Frances
authors.forename: Maite
authors.initials: M
authors.lastname: Garcia
authors.forename: Julio
authors.initials: J
authors.lastname: Escribano
authors.forename: Julian
authors.initials: J
authors.lastname: Garcia-Feijoo
mesh_terms: D000293:Adolescent; D002648:Child; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005902:Glaucoma, Open-Angle / Q000151:congenital / Q000235:genetics*; D006068:Gonioscopy; D006801:Humans; D007429:Intraocular Pressure / Q000235:genetics; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D013030:Spain / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1