Tags

Type your tag names separated by a space and hit enter

PITX2 and FOXC1 spectrum of mutations in ocular syndromes.
Eur J Hum Genet. 2012 Dec; 20(12):1224-33.EJ

Abstract

Anterior segment dysgenesis (ASD) encompasses a broad spectrum of developmental conditions affecting anterior ocular structures and associated with an increased risk for glaucoma. Various systemic anomalies are often observed in ASD conditions such as Axenfeld-Rieger syndrome (ARS) and De Hauwere syndrome. We report DNA sequencing and copy number analysis of PITX2 and FOXC1 in 76 patients with syndromic or isolated ASD and related conditions. PITX2 mutations and deletions were found in 24 patients with dental and/or umbilical anomalies seen in all. Seven PITX2-mutant alleles were novel including c.708_730del, the most C-terminal mutation reported to date. A second case of deletion of the distant upstream but not coding region of PITX2 was identified, highlighting the importance of this recently discovered mechanism for ARS. FOXC1 deletions were observed in four cases, three of which demonstrated hearing and/or heart defects, including a patient with De Hauwere syndrome; no nucleotide mutations in FOXC1 were identified. Review of the literature identified several other patients with 6p25 deletions and features of De Hauwere syndrome. The 1.3-Mb deletion of 6p25 presented here defines the critical region for this phenotype and includes the FOXC1, FOXF2, and FOXQ1 genes. In summary, PITX2 or FOXC1 disruptions explained 63% of ARS and 6% of other ASD in our cohort; all affected patients demonstrated additional systemic defects with PITX2 mutations showing a strong association with dental and/or umbilical anomalies and FOXC1 with heart and hearing defects. FOXC1 deletion was also found to be associated with De Hauwere syndrome.

Authors+Show Affiliations

Department of Pediatrics and Children's Research Institute, Milwaukee, WI, 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 availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22569110

Citation

Reis, Linda M., et al. "PITX2 and FOXC1 Spectrum of Mutations in Ocular Syndromes." European Journal of Human Genetics : EJHG, vol. 20, no. 12, 2012, pp. 1224-33.
Reis LM, Tyler RC, Volkmann Kloss BA, et al. PITX2 and FOXC1 spectrum of mutations in ocular syndromes. Eur J Hum Genet. 2012;20(12):1224-33.
Reis, L. M., Tyler, R. C., Volkmann Kloss, B. A., Schilter, K. F., Levin, A. V., Lowry, R. B., Zwijnenburg, P. J., Stroh, E., Broeckel, U., Murray, J. C., & Semina, E. V. (2012). PITX2 and FOXC1 spectrum of mutations in ocular syndromes. European Journal of Human Genetics : EJHG, 20(12), 1224-33. https://doi.org/10.1038/ejhg.2012.80
Reis LM, et al. PITX2 and FOXC1 Spectrum of Mutations in Ocular Syndromes. Eur J Hum Genet. 2012;20(12):1224-33. PubMed PMID: 22569110.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PITX2 and FOXC1 spectrum of mutations in ocular syndromes. AU - Reis,Linda M, AU - Tyler,Rebecca C, AU - Volkmann Kloss,Bethany A, AU - Schilter,Kala F, AU - Levin,Alex V, AU - Lowry,R Brian, AU - Zwijnenburg,Petra J G, AU - Stroh,Eliza, AU - Broeckel,Ulrich, AU - Murray,Jeffrey C, AU - Semina,Elena V, Y1 - 2012/05/09/ PY - 2012/5/10/entrez PY - 2012/5/10/pubmed PY - 2013/4/30/medline SP - 1224 EP - 33 JF - European journal of human genetics : EJHG JO - Eur. J. Hum. Genet. VL - 20 IS - 12 N2 - Anterior segment dysgenesis (ASD) encompasses a broad spectrum of developmental conditions affecting anterior ocular structures and associated with an increased risk for glaucoma. Various systemic anomalies are often observed in ASD conditions such as Axenfeld-Rieger syndrome (ARS) and De Hauwere syndrome. We report DNA sequencing and copy number analysis of PITX2 and FOXC1 in 76 patients with syndromic or isolated ASD and related conditions. PITX2 mutations and deletions were found in 24 patients with dental and/or umbilical anomalies seen in all. Seven PITX2-mutant alleles were novel including c.708_730del, the most C-terminal mutation reported to date. A second case of deletion of the distant upstream but not coding region of PITX2 was identified, highlighting the importance of this recently discovered mechanism for ARS. FOXC1 deletions were observed in four cases, three of which demonstrated hearing and/or heart defects, including a patient with De Hauwere syndrome; no nucleotide mutations in FOXC1 were identified. Review of the literature identified several other patients with 6p25 deletions and features of De Hauwere syndrome. The 1.3-Mb deletion of 6p25 presented here defines the critical region for this phenotype and includes the FOXC1, FOXF2, and FOXQ1 genes. In summary, PITX2 or FOXC1 disruptions explained 63% of ARS and 6% of other ASD in our cohort; all affected patients demonstrated additional systemic defects with PITX2 mutations showing a strong association with dental and/or umbilical anomalies and FOXC1 with heart and hearing defects. FOXC1 deletion was also found to be associated with De Hauwere syndrome. SN - 1476-5438 UR - https://www.unboundmedicine.com/medline/citation/22569110/PITX2_and_FOXC1_spectrum_of_mutations_in_ocular_syndromes_ L2 - http://dx.doi.org/10.1038/ejhg.2012.80 DB - PRIME DP - Unbound Medicine ER -