Novel mutations in the PITX2 gene in Pakistani and Mexican families with Axenfeld‐Rieger syndrome
Open Access
- 13 May 2020
- journal article
- research article
- Published by Wiley in Molecular Genetics & Genomic Medicine
- Vol. 8 (7), e1215
- https://doi.org/10.1002/mgg3.1215
Abstract
Purpose Axenfeld‐Rieger syndrome (ARS) is a rare autosomal dominant disorder that affects the anterior segment of the eye. The aim of this study was to examine the PITX2 gene to identify possible novel mutations in Pakistani and Mexican families affected by the ARS phenotype. Methods Three unrelated probands with a diagnosis of ARS were recruited for this study. Genomic DNA was isolated from the peripheral blood of the probands and their family members. Polymerase chain reaction and Sanger sequencing were used for the analysis of coding exons and the flanking intronic regions of the PITX2 gene. Bioinformatics tools and database (VarSome, Provean, and MutationTaster, SIFT, PolyPhen‐2, and HOPE) were evaluated to explore missense variants. Results We identified novel heterozygous variations in the PITX2 gene that segregated with the ARS phenotype within the families. The variant NM_153426.2(PITX2):c.226G > T or p.(Ala76Ser) and the mutation NM_153426.2(PITX2):c.455G > A or p.(Cys152Tyr) were identified in two Pakistani pedigrees, and the mutation NM_153426.2(PITX2):c.242_265del or p.(Lys81_Gln88del), segregated in a Mexican family. Conclusion Our study extends the spectrum of PITX2 mutations in individuals with ARS, enabling an improved diagnosis of this rare but serious syndrome.Keywords
Funding Information
- European Union Horizon 2020 Research and Innovation program under the Marie Skłodowska-Curie (675033)
This publication has 37 references indexed in Scilit:
- Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfacesBMC Bioinformatics, 2010
- Clinical utility gene card for: Axenfeld–Rieger syndromeEuropean Journal of Human Genetics, 2010
- Duplication of MAOA, MAOB, and NDP in a patient with mental retardation and epilepsyEuropean Journal of Human Genetics, 2010
- Using SIFT and PolyPhen to Predict Loss-of-Function and Gain-of-Function MutationsGenetic Testing and Molecular Biomarkers, 2010
- Axenfeld-Rieger Syndrome Associated with Congenital Glaucoma and Cytochrome P4501B1 Gene MutationsCase Reports in Medicine, 2010
- Axenfeld–Rieger syndrome and spectrum of PITX2 and FOXC1 mutationsEuropean Journal of Human Genetics, 2009
- Analysis of Mutations of thePITX2Transcription Factor Found in Patients with Axenfeld-Rieger SyndromeInvestigative Ophthalmology & Visual Science, 2009
- An unusual class of PITX2 mutations in Axenfeld‐Rieger syndromeBirth Defects Research Part A: Clinical and Molecular Teratology, 2006
- Identification of a Dominant Negative Homeodomain Mutation in Rieger SyndromeOnline Journal of Public Health Informatics, 2001
- Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndromeNature Genetics, 1996