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A family with Axenfeld-Rieger syndrome and Peters Anomaly caused by a point mutation (Phe112Ser) in the FOXC1 gene.
Am J Ophthalmol. 2003 Mar; 135(3):368-75.AJ

Abstract

PURPOSE

Mutations of the forkhead transcription factor gene FOXC1 result in anterior segment anomalies. No description of the spectrum of defects resulting from a single point mutation of this gene exists in the ophthalmology literature. We have screened all available patients with Axenfeld-Rieger genes (PITX2 and FOXC1). In this report, we clinically characterize the spectrum of ocular and systemic manifestations in one family resulting from a previously reported point mutation (Phe112Ser) in FOXC1.

DESIGN

Observational case series.

METHODS

Ten members of a multigenerational family were examined for signs of glaucoma, anterior segment abnormalities, and systemic features of Axenfeld-Rieger syndrome. The examinations were performed in an ophthalmology examination room or in the patients' homes. Blood was obtained from 10 members and screened for mutations in FOXC1 using direct DNA sequencing.

RESULTS

A single mutation causing a T to C change in codon 112 (Phe112Ser) of FOXC1 was present in six members of the family. Five of these six patients were examined and all demonstrated anterior segment anomalies. One patient had Axenfeld anomaly, one had Rieger syndrome, and one had both Axenfeld anomaly and Peters anomaly. Additionally, some members demonstrated cardiac abnormalities, which may be secondary to their FOXC1 mutation.

CONCLUSIONS

A wide spectrum of clinical phenotypes can result from a single point mutation of FOXC1. This report confirms that Rieger syndrome (with dental and facial abnormalities) can be caused by a mutation in FOXC1. It is also the first report of Peters anomaly being caused by a FOXC1 mutation.

Authors+Show Affiliations

Department of Ophthalmology, Howard Hughes Medical Institute, The University of Iowa, Iowa City, Iowa, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12614756

Citation

Honkanen, Robert A., et al. "A Family With Axenfeld-Rieger Syndrome and Peters Anomaly Caused By a Point Mutation (Phe112Ser) in the FOXC1 Gene." American Journal of Ophthalmology, vol. 135, no. 3, 2003, pp. 368-75.
Honkanen RA, Nishimura DY, Swiderski RE, et al. A family with Axenfeld-Rieger syndrome and Peters Anomaly caused by a point mutation (Phe112Ser) in the FOXC1 gene. Am J Ophthalmol. 2003;135(3):368-75.
Honkanen, R. A., Nishimura, D. Y., Swiderski, R. E., Bennett, S. R., Hong, S., Kwon, Y. H., Stone, E. M., Sheffield, V. C., & Alward, W. L. (2003). A family with Axenfeld-Rieger syndrome and Peters Anomaly caused by a point mutation (Phe112Ser) in the FOXC1 gene. American Journal of Ophthalmology, 135(3), 368-75.
Honkanen RA, et al. A Family With Axenfeld-Rieger Syndrome and Peters Anomaly Caused By a Point Mutation (Phe112Ser) in the FOXC1 Gene. Am J Ophthalmol. 2003;135(3):368-75. PubMed PMID: 12614756.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A family with Axenfeld-Rieger syndrome and Peters Anomaly caused by a point mutation (Phe112Ser) in the FOXC1 gene. AU - Honkanen,Robert A, AU - Nishimura,Darryl Y, AU - Swiderski,Ruth E, AU - Bennett,Steven R, AU - Hong,Sungpyo, AU - Kwon,Young H, AU - Stone,Edwin M, AU - Sheffield,Val C, AU - Alward,Wallace L M, PY - 2003/3/5/pubmed PY - 2003/3/18/medline PY - 2003/3/5/entrez SP - 368 EP - 75 JF - American journal of ophthalmology JO - Am J Ophthalmol VL - 135 IS - 3 N2 - PURPOSE: Mutations of the forkhead transcription factor gene FOXC1 result in anterior segment anomalies. No description of the spectrum of defects resulting from a single point mutation of this gene exists in the ophthalmology literature. We have screened all available patients with Axenfeld-Rieger genes (PITX2 and FOXC1). In this report, we clinically characterize the spectrum of ocular and systemic manifestations in one family resulting from a previously reported point mutation (Phe112Ser) in FOXC1. DESIGN: Observational case series. METHODS: Ten members of a multigenerational family were examined for signs of glaucoma, anterior segment abnormalities, and systemic features of Axenfeld-Rieger syndrome. The examinations were performed in an ophthalmology examination room or in the patients' homes. Blood was obtained from 10 members and screened for mutations in FOXC1 using direct DNA sequencing. RESULTS: A single mutation causing a T to C change in codon 112 (Phe112Ser) of FOXC1 was present in six members of the family. Five of these six patients were examined and all demonstrated anterior segment anomalies. One patient had Axenfeld anomaly, one had Rieger syndrome, and one had both Axenfeld anomaly and Peters anomaly. Additionally, some members demonstrated cardiac abnormalities, which may be secondary to their FOXC1 mutation. CONCLUSIONS: A wide spectrum of clinical phenotypes can result from a single point mutation of FOXC1. This report confirms that Rieger syndrome (with dental and facial abnormalities) can be caused by a mutation in FOXC1. It is also the first report of Peters anomaly being caused by a FOXC1 mutation. SN - 0002-9394 UR - https://www.unboundmedicine.com/medline/citation/12614756/A_family_with_Axenfeld_Rieger_syndrome_and_Peters_Anomaly_caused_by_a_point_mutation__Phe112Ser__in_the_FOXC1_gene_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002939402020615 DB - PRIME DP - Unbound Medicine ER -