Whole exome sequencing identifies multiple diagnoses in congenital glaucoma with systemic anomalies.

Autor: Reis LM; Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, WI, USA., Tyler RC; Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, WI, USA., Weh E; Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, WI, USA.; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA., Hendee KE; Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, WI, USA.; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA., Schilter KF; Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, WI, USA.; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA., Phillips JA 3rd; Division of Medical Genetics and Genomic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Sequeira S; Metabolic Unit, Pediatric Department, Hospital de Dona Estefânia, CHLC, Lisbon, Portugal., Schinzel A; Department of Genetics, Institute of Medical Genetics, Schwerzenbach, Switzerland., Semina EV; Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, WI, USA. esemina@mcw.edu.; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA. esemina@mcw.edu.; Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, WI, USA. esemina@mcw.edu.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2016 Oct; Vol. 90 (4), pp. 378-82. Date of Electronic Publication: 2016 Jul 12.
DOI: 10.1111/cge.12816
Abstrakt: The genetic basis of congenital glaucoma with systemic anomalies is largely unknown. Whole exome sequencing (WES) in 10 probands with congenital glaucoma and variable systemic anomalies identified pathogenic or likely pathogenic variants in three probands; in two of these, a combination of two Mendelian disorders was found to completely explain the patients' features whereas in the third case only the ocular findings could be explained by the genetic diagnosis. The molecular diagnosis for glaucoma included two cases with compound heterozygous or homozygous pathogenic alleles in CYP1B1 and one family with a dominant pathogenic variant in FOXC1; the second genetic diagnosis for the additional systemic features included compound heterozygous mutations in NPHS1 in one family and a heterozygous 18q23 deletion in another pedigree. These findings show the power of WES in the analysis of complex conditions and emphasize the importance of CYP1B1 screening in patients with congenital glaucoma regardless of the presence/absence of other systemic anomalies.
Competing Interests: The authors declare that they have no conflict of interest.
(© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE