Journal article
PITX2 and FOXC1 spectrum of mutations in ocular syndromes
European journal of human genetics : EJHG, Vol.20(12), pp.1224-1233
12/2012
DOI: 10.1038/ejhg.2012.80
PMCID: PMC3499749
PMID: 22569110
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.
Details
- Title: Subtitle
- PITX2 and FOXC1 spectrum of mutations in ocular syndromes
- Creators
- Linda M Reis - , Milwaukee, WIRebecca C Tyler - , Milwaukee, WIBethany A Volkmann Kloss - , Milwaukee, WIKala F Schilter - , Milwaukee, WIAlex V Levin - , Philadelphia, PAR Brian Lowry - , Calgary, ABPetra J G Zwijnenburg - , Amsterdam, HVEliza Stroh - , Philadelphia, PAUlrich Broeckel - , Milwaukee, WIJeffrey C Murray - , Iowa City, IAElena V Semina - , Milwaukee, WI
- Resource Type
- Journal article
- Publication Details
- European journal of human genetics : EJHG, Vol.20(12), pp.1224-1233
- DOI
- 10.1038/ejhg.2012.80
- PMID
- 22569110
- PMCID
- PMC3499749
- NLM abbreviation
- Eur J Hum Genet
- ISSN
- 1018-4813
- eISSN
- 1476-5438
- Publisher
- Nature Publishing Group
- Alternative title
- PITX2 and FOXC1 mutations in ocular syndromes
- Language
- English
- Date published
- 12/2012
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025361202771
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