Abstract

Objective: To study the clinicopathological features of Oto palato digital syndrome type II (OPD-II) and telomere length maintenance pathway. Design: Case-control study of OPD-II. Setting: Different clinicopathological studies along with telomere length maintenance pathways were investigated. Participants: Clinically diagnosed two OPD-II patients and four randomly selected age-matched normal individual. Main outcome measures: Studied OstiumSecondum Atrial Septal Defects (osASD) by ECG, testes image by USG, subcortical dysrythmia by EEG, image of corpus callosum by MRI, 17 α oH progesterone level in blood. telomere length, expression of telomerase and telomere-associated genes of PBMC were also measured. Results: Two children with OPD-II showed characteristic clinical symptoms such as cleft palate, broad forehead, facial dysmorphism, flat nasal bridge, low birth weight but no abnormality of the digits. The patient-1 exhibited osASD, bilateral undescended testes with hypospadiusand eventually developed seizure disorder in the follow up, ambiguous genitalia and high level of 17 α oH progesterone in blood. Interestingly, this patient showed shorter telomere length of PBMC – (~60%), low (<4%) expression of hTERT and hTERC compared with control group implicating that patient-1 had inactive telomerase. We observed de-regulated expression of all six shelterin proteins and two non-shelterin proteins such as BTBD12 and PARP-1, indicating the dysfunctional telomere of the patient-1. The patient-2 exhibits similar facial dysmorphism and absent corpus callosum as detected by MRI. Conclusions: OPD-II patients showed osASD, subcortical dysrythmia, thin corpus callosum, undescended testes and higher 17 α oH progesterone level in blood. Patient-1 also showed short telomere, inactive telomerase and dysfunctional telomere.>