Novel mutations in the PITX2 gene in Pakistani and Mexican families with Axenfeld‐Rieger syndrome. Issue 7 (13th May 2020)

• Record Type: Journal Article
• Authors: Lo Faro, Valeria; Siddiqui, Sorath N.; Khan, Muhammad I.; Villanueva‐Mendoza, Cristina; Cortés‐González, Vianney; Jansonius, Nomdo; Bergen, Arthur A. B.; Micheal, Shazia
• Is Part Of: Molecular genetics & genomic medicine. Volume 8:Issue 7(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-05-13
• Subjects: anterior segment dysgenesis -- Axenfeld‐Rieger -- mutations -- PITX2; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.1215
• Languages: English
• ISSNs: 2324-9269

Abstract

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. Abstract : The authors report clinical data on patients presenting with Axenfeld‐Rieger syndrome (ARS) from three families. Molecular genetic studies identified novel heterozygous sequence variants in the PITX2 gene that are the likely causes of the disease in the respective families.