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Xiaohui Zhang, Jieqiong Chen, Ke Xu, Yang Li; Identification two novel PITX2 gene mutations in Chinese patients with distinct ocular phenotypes in Axenfeld-Rieger syndrome. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6415.
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Axenfeld-Rieger syndrome (ARS) is an autosomal dominant condition characterized by a variable combination of anterior segment dysgenesis, dental anomalies, and umbilical hernia. Reports have shown that PITX2 (paired-like homeodomain 2) gene mutations mainly accounts for ARS. Here we describe two Chinese families affected by ARS and characterize their disease-causing gene mutation.
According to guidelines approved by the Beijing Tongren Ethics Committee and the Declaration of Helsinki, Probands of three families underwent a complete eye examination. After informed consent blood samples were obtained, and DNA was extracted of all participants. PITX2 gene mutations were screened by direct DNA sequencing. Whenever substitutions were identified in a patient, restriction fragment length polymorphism analysis (RFLP) was performed on all available family members and 100 normal controls. Bioinformatics analysis was undergone by the PolyPhen (polymorphism phenotyping) programs to predict the effect of mutations detected on the function of PITX2 protein.
Two of three familial cases with anterior segment dysgenesis phenotypes were found PITX2 novel mutations, a indel mutation c.348_352del(AGAAA)insTTCT and a nonsense mutation at codon 96 (p.Q96X). These two novel mutations cosegregated with the affected members in their family and not present in the unaffected family members or 100 normal controls.
The proband of family with nonsense mutation of PITX2 gene exhibits retinal detachment in her right eye which was more severe than the other family. Both of mutations lay within the homeodomain of PITX2. Our results further confirm that the homeodomain is the mutational hot region for PITX2.
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