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

Autor:	Blue EE; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, Washington, USA.; Brotman-Baty Institute for Precision Medicine, Seattle, Washington, USA., Moore KJ; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., North KE; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Desrosiers TA; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Carmichael SL; Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA., White JJ; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington, USA., Chong JX; Brotman-Baty Institute for Precision Medicine, Seattle, Washington, USA.; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington, USA., Bamshad MJ; Brotman-Baty Institute for Precision Medicine, Seattle, Washington, USA.; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington, USA.; Division of Genetic Medicine, Seattle Children's Hospital, Seattle, Washington, USA.; Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA., Jenkins MM; National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA., Almli LM; National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA., Brody LC; Division of Genomics and Society, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA., Freedman SF; Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA., Reefhuis J; National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA., Romitti PA; Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, Iowa, USA., Shaw GM; Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA., Werler M; Department of Epidemiology, School of Public Health, Boston University, Boston, Massachusetts, USA.; Slone Epidemiology Center at Boston University, Boston, Massachusetts, USA., Kay DM; Division of Genetics, Wadsworth Center, New York State Department of Health, Albany, New York, USA., Browne ML; New York State Department of Health, Birth Defects Registry, Albany, New York, USA.; Department of Epidemiology and Biostatistics, University at Albany School of Public Health, Rensselaer, New York, USA., Feldkamp ML; Division of Medical Genetics, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA., Finnell RH; Center for Precision Environmental Health, Departments of Molecular and Cellular Biology and Medicine, Baylor College of Medicine, Houston, Texas, USA., Nembhard WN; Department of Epidemiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA., Pangilinan F; Division of Genomics and Society, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA., Olshan AF; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Jazyk:	angličtina
Zdroj:	Birth defects research [Birth Defects Res] 2024 Jul; Vol. 116 (7), pp. e2384.
DOI:	10.1002/bdr2.2384
Abstrakt:	Background: Primary congenital glaucoma (PCG) affects approximately 1 in 10,000 live born infants in the United States (U.S.). 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 U.S., suggesting that alternative genes may contribute to the condition. This study utilized exome sequencing to investigate the genetic architecture of PCG in the U.S. 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 U.S. 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 (five 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. (© 2024 Wiley Periodicals LLC.)
Databáze:	MEDLINE
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