Exome sequencing identifies novel genes underlying primary congenital glaucoma in the National Birth Defects Prevention Study

Details

• Alternative Title:
  Birth Defects Res
• Personal Author:
  Blue, Elizabeth E. ; Moore, Kristin J. ; North, Kari E. ; Desrosiers, Tania A. ; Carmichael, Suzan L. ; White, Janson J. ; Chong, Jessica X. ; Bamshad, Michael J. ; Jenkins, Mary M. ; Almli, Lynn M. ; Brody, Lawrence C. ; Freedman, Sharon F. ; Reefhuis, Jennita ; Romitti, Paul A. ; Shaw, Gary M. ; Werler, Martha ; Kay, Denise M. ; Browne, Marilyn L. ; Feldkamp, Marcia L. ; Finnell, Richard H. ; Nembhard, Wendy N. ; Pangilinan, Faith ; Olshan, Andrew F.
• Corporate Authors:
  National Institutes of Health Intramural Sequencing Center ; University of Washington Center for Mendelian Genomics ; National Birth Defects Prevention Study
• Description:
  Background:
  
  Primary congenital glaucoma (PCG) affects approximately 1 in 10,000 live born infants in the United States (US). PCG has a autosomal recessive inheritance pattern, and variable expressivity and reduced penetrance have been reported. Likely causal variants in the most commonly mutated gene, CYP1B1, are less prevalent in the US, suggesting that alternative genes may contribute to the condition. This study utilized exome sequencing to investigate the genetic architecture of PCG in the US and to identify novel genes and variants.
  
  Methods:
  
  We studied 37 family trios where infants had PCG and were part of the National Birth Defects Prevention Study (births 1997–2011), a US multicenter study of birth defects. Samples underwent exome sequencing and sequence reads were aligned to the human reference sample (NCBI build 37/hg19). Variant filtration was conducted under de novo and Mendelian inheritance models using GEMINI.
  
  Results:
  
  Among candidate variants, CYP1B1 was most represented (5 trios, 13.5%). Twelve probands (32%) had potentially pathogenic variants in other genes not previously linked to PCG but important in eye development and/or to underlie Mendelian conditions with potential phenotypic overlap (e.g., CRYBB2, RXRA, GLI2).
  
  Conclusion:
  
  Variation in the genes identified in this population-based study may help to further explain the genetics of PCG.
  
  
• Subjects:
  Cytochrome P-450 CYP1B1 Exome Exome Sequencing Female Genetic Predisposition To Disease Glaucoma Humans Infant Infant, Newborn Male Mutation United States

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• Keywords:
  Birth Defects Congenital Glaucoma CYP1B1 Genetics Mutations Newborn Eye Abnormalities
• Source:
  Birth Defects Res. 116(7):e2384
• Pubmed ID:
  38990107
• Pubmed Central ID:
  PMC11245170
• Document Type:
  Journal Article
• Funding:
  U01 DD001308/DD/NCBDD CDC HHSUnited States/ ; CDP 13-003/HX/HSRD VAUnited States/ ; U24 HG011746/HG/NHGRI NIH HHSUnited States/ ; U01 DD001231/DD/NCBDD CDC HHSUnited States/ ; FOA #DD13-003/CC/CDC HHSUnited States/ ; U01DD001231/CC/CDC HHSUnited States/ ; PA #96043/CC/CDC HHSUnited States/ ; U01 HG011744/HG/NHGRI NIH HHSUnited States/ ; EP-D-18-001/EPA/EPAUnited States/ ; UM1 HG006493/HG/NHGRI NIH HHSUnited States/ ; NOFO #DD18-001/CC/CDC HHSUnited States/ ; U01 DD001036/DD/NCBDD CDC HHSUnited States/ ; FOA #DD09-001/CC/CDC HHSUnited States/ ; U01DD001231/ACL/ACL HHSUnited States/ ; U01 DD000488/DD/NCBDD CDC HHSUnited States/ ; U24 HG008956/HG/NHGRI NIH HHSUnited States/ ; PA #02081/CC/CDC HHSUnited States/
• Volume:
  116
• Issue:
  7
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:5aa9910a284f29f47e7a0062f2ff014a07b3a008313a8a1cdb94352b8dfebef242e74a9dd829274812f02c4d586e3568c713a4caf11142e16e8cea3994576a90
• Download URL:
  https://stacks.cdc.gov/view/cdc/158695/cdc_158695_DS1.pdf
• File Type:
  [PDF - 402.59 KB ]