title: Carrier frequency of CYP1B1 mutations in the United States (an American Ophthalmological Society thesis).
abstract: OBJECTIVE
  CYP1B1 mutations cause autosomal recessive congenital glaucoma. Disease risk assessment for families with CYP1B1 mutations requires knowledge of the population mutation carrier frequency. The purpose of this study is to determine the CYP1B1 mutation carrier frequency in clinically normal individuals residing in the United States. Because CYP1B1 mutations can exhibit variable expressivity, we hypothesize that the mutation carrier frequency is higher than expected.
  
  
  METHODS
  Two hundred fifty individuals without glaucoma or a family history of glaucoma were enrolled. CYP1B1 mutations were identified by DNA sequencing, and pathogenicity was estimated by PolyPhen-2 or a previous report of disease causality.
  
  
  RESULTS
  Based on the disease frequency (1 in 10,000) and prevalence of CYP1B1-related congenital glaucoma (15% to 20%), the frequency of CYP1B1-related congenital glaucoma in the United States is approximately 1 in 50,000. Assuming Hardy-Weinberg equilibrium, the expected CYP1B1 mutation carrier frequency would be 1 in 112, or 0.89%. Among the 250 study participants, 11 (4.4%) are carriers of a single pathogenic mutation, representing a carrier frequency of 1 in 22, which is 5.1 times the expected frequency. A higher-than-expected carrier frequency (1 in 33, 3.0%) was also observed in 4300 white individuals sequenced by the National Heart Lung and Blood Institute Exome Sequencing Project.
  
  
  CONCLUSIONS
  Our results show that the CYP1B1 mutation carrier frequency in the US population is between 1 in 22 and 1 in 33, which is 5.1 to 3.4 times the expected frequency. These results suggest that more individuals than expected are carriers of a deleterious CYP1B1 mutation, and that the prevalence of CYP1B1-related disease may be higher than expected.
authors: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston Massachusetts.
authors: Janey L
authors: JL
authors: Wiggs
authors: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston Massachusetts.
authors: Anne M
authors: AM
authors: Langgurth
authors: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston Massachusetts.
authors: Keri F
authors: KF
authors: Allen
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005901:Glaucoma / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D011446:Prospective Studies; D014481:United States / Q000453:epidemiology
chemical_list: C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1
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