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A Novel Homozygous Mutation in FOXC1 Causes Axenfeld Rieger Syndrome with Congenital Glaucoma.
PLoS One. 2016; 11(7):e0160016.Plos

Abstract

BACKGROUND

Anterior segment dysgenesis (ASD) disorders are a group of clinically and genetically heterogeneous phenotypes in which frequently cornea, iris, and lens are affected. This study aimed to identify novel mutations in PAX6, PITX2 and FOXC1 in families with anterior segment dysgenesis disorders.

METHODS

We studied 14 Pakistani and one Mexican family with Axenfeld Rieger syndrome (ARS; n = 10) or aniridia (n = 5). All affected and unaffected family members underwent full ophthalmologic and general examinations. Total genomic DNA was isolated from peripheral blood. PCR and Sanger sequencing were performed for the exons and intron-exon boundaries of the FOXC1, PAX6, and PITX2 genes.

RESULTS

Mutations were identified in five of the 15 probands; four variants were novel and one variant was described previously. A novel de novo variant (c.225C>A; p.Tyr75*) was identified in the PAX6 gene in two unrelated probands with aniridia. In addition, a known variant (c.649C>T; p.Arg217*) in PAX6 segregated in a family with aniridia. In the FOXC1 gene, a novel heterozygous variant (c.454T>C; p.Trp152Arg) segregated with the disease in a Mexican family with ARS. A novel homozygous variant (c.92_100del; p.Ala31_Ala33del) in the FOXC1 gene segregated in a Pakistani family with ARS and congenital glaucoma.

CONCLUSIONS

Our study expands the mutation spectrum of the PAX6 and FOXC1 genes in individuals with anterior segment dysgenesis disorders. In addition, our study suggests that FOXC1 mutations, besides typical autosomal dominant ARS, can also cause ARS with congenital glaucoma through an autosomal recessive inheritance pattern. Our results thus expand the disease spectrum of FOXC1, and may lead to a better understanding of the role of FOXC1 in development.

Authors+Show Affiliations

Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.Department of Pediatric Ophthalmology, Al-Shifa Eye Trust Hospital, Jhelum Road, Rawalpindi, Pakistan.Department of Pediatric Ophthalmology, Al-Shifa Eye Trust Hospital, Jhelum Road, Rawalpindi, Pakistan.Genetics Department Asociación Para Evitar la Ceguera en México, Coyoacán, Mexico.Genetics Department Asociación Para Evitar la Ceguera en México, Coyoacán, Mexico.Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands. Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27463523

Citation

Micheal, Shazia, et al. "A Novel Homozygous Mutation in FOXC1 Causes Axenfeld Rieger Syndrome With Congenital Glaucoma." PloS One, vol. 11, no. 7, 2016, pp. e0160016.
Micheal S, Siddiqui SN, Zafar SN, et al. A Novel Homozygous Mutation in FOXC1 Causes Axenfeld Rieger Syndrome with Congenital Glaucoma. PLoS One. 2016;11(7):e0160016.
Micheal, S., Siddiqui, S. N., Zafar, S. N., Villanueva-Mendoza, C., Cortés-González, V., Khan, M. I., & den Hollander, A. I. (2016). A Novel Homozygous Mutation in FOXC1 Causes Axenfeld Rieger Syndrome with Congenital Glaucoma. PloS One, 11(7), e0160016. https://doi.org/10.1371/journal.pone.0160016
Micheal S, et al. A Novel Homozygous Mutation in FOXC1 Causes Axenfeld Rieger Syndrome With Congenital Glaucoma. PLoS One. 2016;11(7):e0160016. PubMed PMID: 27463523.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Novel Homozygous Mutation in FOXC1 Causes Axenfeld Rieger Syndrome with Congenital Glaucoma. AU - Micheal,Shazia, AU - Siddiqui,Sorath Noorani, AU - Zafar,Saemah Nuzhat, AU - Villanueva-Mendoza,Cristina, AU - Cortés-González,Vianney, AU - Khan,Muhammad Imran, AU - den Hollander,Anneke I, Y1 - 2016/07/27/ PY - 2016/05/04/received PY - 2016/07/12/accepted PY - 2016/7/28/entrez PY - 2016/7/28/pubmed PY - 2017/7/25/medline SP - e0160016 EP - e0160016 JF - PloS one JO - PLoS One VL - 11 IS - 7 N2 - BACKGROUND: Anterior segment dysgenesis (ASD) disorders are a group of clinically and genetically heterogeneous phenotypes in which frequently cornea, iris, and lens are affected. This study aimed to identify novel mutations in PAX6, PITX2 and FOXC1 in families with anterior segment dysgenesis disorders. METHODS: We studied 14 Pakistani and one Mexican family with Axenfeld Rieger syndrome (ARS; n = 10) or aniridia (n = 5). All affected and unaffected family members underwent full ophthalmologic and general examinations. Total genomic DNA was isolated from peripheral blood. PCR and Sanger sequencing were performed for the exons and intron-exon boundaries of the FOXC1, PAX6, and PITX2 genes. RESULTS: Mutations were identified in five of the 15 probands; four variants were novel and one variant was described previously. A novel de novo variant (c.225C>A; p.Tyr75*) was identified in the PAX6 gene in two unrelated probands with aniridia. In addition, a known variant (c.649C>T; p.Arg217*) in PAX6 segregated in a family with aniridia. In the FOXC1 gene, a novel heterozygous variant (c.454T>C; p.Trp152Arg) segregated with the disease in a Mexican family with ARS. A novel homozygous variant (c.92_100del; p.Ala31_Ala33del) in the FOXC1 gene segregated in a Pakistani family with ARS and congenital glaucoma. CONCLUSIONS: Our study expands the mutation spectrum of the PAX6 and FOXC1 genes in individuals with anterior segment dysgenesis disorders. In addition, our study suggests that FOXC1 mutations, besides typical autosomal dominant ARS, can also cause ARS with congenital glaucoma through an autosomal recessive inheritance pattern. Our results thus expand the disease spectrum of FOXC1, and may lead to a better understanding of the role of FOXC1 in development. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/27463523/A_Novel_Homozygous_Mutation_in_FOXC1_Causes_Axenfeld_Rieger_Syndrome_with_Congenital_Glaucoma_ DB - PRIME DP - Unbound Medicine ER -