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Novel mutations in the PITX2 gene in Pakistani and Mexican families with Axenfeld-Rieger syndrome.
Mol Genet Genomic Med. 2020 07; 8(7):e1215.MG

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.

Authors+Show Affiliations

Department of Clinical Genetics, University Medical Center (UMC), University of Amsterdam (UvA), Amsterdam, The Netherlands. Department of Ophthalmology, University Medical Center Groningen (UMCG), University of Groningen (RUG), Groningen, The Netherlands.Department of Pediatric Ophthalmology and Strabismus, Al-Shifa Eye Trust Hospital, Rawalpindi, Pakistan.Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud UMC, Nijmegen, The Netherlands.Department of Genetics, Asociación Para Evitar la Ceguera en México, México, México.Department of Genetics, Asociación Para Evitar la Ceguera en México, México, México.Department of Ophthalmology, University Medical Center Groningen (UMCG), University of Groningen (RUG), Groningen, The Netherlands.Department of Clinical Genetics, University Medical Center (UMC), University of Amsterdam (UvA), Amsterdam, The Netherlands. Department of Ophthalmology, Universitair Medische Centre (UMC), University of Amsterdam (UvA), Amsterdam, The Netherlands. The Netherlands Institute for Neurosciences (NIN-KNAW), Amsterdam, The Netherlands.Department of Clinical Genetics, University Medical Center (UMC), University of Amsterdam (UvA), Amsterdam, The Netherlands.

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32400113

Citation

Lo Faro, Valeria, et al. "Novel Mutations in the PITX2 Gene in Pakistani and Mexican Families With Axenfeld-Rieger Syndrome." Molecular Genetics & Genomic Medicine, vol. 8, no. 7, 2020, pp. e1215.
Lo Faro V, Siddiqui SN, Khan MI, et al. Novel mutations in the PITX2 gene in Pakistani and Mexican families with Axenfeld-Rieger syndrome. Mol Genet Genomic Med. 2020;8(7):e1215.
Lo Faro, V., Siddiqui, S. N., Khan, M. I., Villanueva-Mendoza, C., Cortés-González, V., Jansonius, N., Bergen, A. A. B., & Micheal, S. (2020). Novel mutations in the PITX2 gene in Pakistani and Mexican families with Axenfeld-Rieger syndrome. Molecular Genetics & Genomic Medicine, 8(7), e1215. https://doi.org/10.1002/mgg3.1215
Lo Faro V, et al. Novel Mutations in the PITX2 Gene in Pakistani and Mexican Families With Axenfeld-Rieger Syndrome. Mol Genet Genomic Med. 2020;8(7):e1215. PubMed PMID: 32400113.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel mutations in the PITX2 gene in Pakistani and Mexican families with Axenfeld-Rieger syndrome. AU - Lo Faro,Valeria, AU - Siddiqui,Sorath N, AU - Khan,Muhammad I, AU - Villanueva-Mendoza,Cristina, AU - Cortés-González,Vianney, AU - Jansonius,Nomdo, AU - Bergen,Arthur A B, AU - Micheal,Shazia, Y1 - 2020/05/13/ PY - 2020/01/06/received PY - 2020/02/12/revised PY - 2020/02/24/accepted PY - 2020/5/14/pubmed PY - 2021/5/1/medline PY - 2020/5/14/entrez KW - Axenfeld-Rieger KW - PITX2 KW - anterior segment dysgenesis KW - mutations SP - e1215 EP - e1215 JF - Molecular genetics & genomic medicine JO - Mol Genet Genomic Med VL - 8 IS - 7 N2 - 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. SN - 2324-9269 UR - https://www.unboundmedicine.com/medline/citation/32400113/Novel_mutations_in_the_PITX2_gene_in_Pakistani_and_Mexican_families_with_Axenfeld_Rieger_syndrome_ DB - PRIME DP - Unbound Medicine ER -