In our patient, compound heterozygosity with PLOD2 mutations is associated with a clinical phenotype distinctive from classic BRKS2 indicating that when COL1A1 and COL1A2 mutation testing is negative for OI without congenital contractures or pterygia, atypical BRKS should be considered.
Bruck syndrome type 2 (BRKS2; MIM:609220) is a rare form of autosomal recessive OI caused by biallelic PLOD2 variants and is associated with congenital joint contractures with pterygia.
There were no significant differences between pterygium and control groups in age, sex, and distribution of genotype and allelic frequency of VEGF-460 polymorphism.
Several researchers believe that pterygium is UV-related and that abnormal expression of p53 protein and infection with human papillomavirus (HPV) are risk factors for pterygium, but their experiments have been inconclusive.
Other findings in pterygium include the frequent detection of HPV DNA, ocular surface changes such as the overexpression of various proteins, including defensins and phospolipases D, as well as the up-regulation of growth factors, such as bFGF or VEGF.
Therefore, BPDE-like DNA adduct, p53 protein expression and p53 gene mutation were examined in this study to provide more molecular evidence to understand the cause of p53 gene mutation in pterygium.
In analysis of specimens from pterygium patients as well as normal conjunctivas, VEGF121 and VEGF165 were identified as the only VEGF splice forms expressed.
These studies indicate that tumor suppressor gene p53 and other genes associated with DNA repair, cell proliferation, migration and angiogenesis are critical for the development of pterygium.
Antibodies raised against VEGF and p53 were used to analyze the distribution and expression of these markers in pterygium and normal human conjunctiva were used as negative control.
Molecular genetic alterations reported in association with pterygium include loss of heterozygosity (LOH), point mutations of proto-oncogenes, such as K-ras and alterations in the expression of tumor suppressor genes, such as p53 or p63.
HPV 16/18 E6 contributes to HPV-mediated pterygium pathogenesis as it is partly involved in p53 inactivation and is expressed in HPV DNA-positive pterygium.
Our study demonstrated that inactivation of p53 in pterygium may influence miR-200a, resulting in ZEB1/ZEB2 up-regulation and EMT processing of pterygium.