Deleterious Variants in WNT10A, EDAR, and EDA Causing Isolated and Syndromic Tooth Agenesis: A Structural Perspective from Molecular Dynamics Simulations.

The dental abnormalities are the typical features of many ectodermal dysplasias along with congenital malformations of nails, skin, hair, and sweat glands. However, several reports of non-syndromic/isolated tooth agenesis have also been found in the literature. The characteristic features of hypohidrotic ectodermal dysplasia (HED) comprise of hypodontia/oligodontia, along with hypohidrosis/anhidrosis, and hypotrichosis. Pathogenic variants in EDA, EDAR, EDARADD, and TRAF6, cause the phenotypic expression of HED. Genetic alterations in EDA and WNT10A cause particularly non-syndromic/isolated oligodontia. In the current project, we recruited 57 patients of 17 genetic pedigrees (A-Q) from different geographic regions of the world, including Pakistan, Egypt, Saudi Arabia, and Syria. The molecular investigation of different syndromic and non-syndromic dental conditions, including hypodontia, oligodontia, generalized odontodysplasia, and dental crowding was carried out by using exome and Sanger sequencing. We have identified a novel missense variant (c.311G>A; p.Arg104His) in WNT10A in three oligodontia patients of family A, two novel sequence variants (c.207delinsTT, p.Gly70Trpfs*25 and c.1300T>G; p.Try434Gly) in EDAR in three patients of family B and four patients of family C, respectively. To better understand the structural and functional consequences of missense variants in WNT10A and EDAR on the stability of the proteins, we have performed extensive molecular dynamic (MD) simulations. We have also identified three previously reported pathogenic variants (c.1076T>C; p.Met359Thr), (c.1133C>T; p.Thr378Met) and (c.594_595insC; Gly201Argfs*39) in EDA in family D (four patients), E (two patients) and F (one patient), correspondingly. Presently, our data explain the genetic cause of 18 syndromic and non-syndromic tooth agenesis patients in six autosomal recessive and X-linked pedigrees (A-F), which expand the mutational spectrum of these unique clinical manifestations.

Frequency of hepatitis C in asymptomatic patients in District Headquarters Hospital Kotli, Azad Kashmir.

BACKGROUND: Hepatitis C is a common problem in developing world. It can affect a large number of asymptomatic people in whom it may cause serious complications in long run. Moreover, these asymptomatic infected people pose a serious risk for the transmission of infection to healthy population. Objective of this study was to estimate the frequency of Hepatitis C in asymptomatic adult patients attending medical OPD of District Headquarters Hospital Kotli, Azad Kashmir, and to assess the risk factors associated with its transmission. METHODS: This was a cross-sectional study that included asymptomatic patients of both genders, aged 15-80 years, attending medical OPD of District Headquarter Hospital Kotli, Azad Kashmir from January to December, 2008. They attended the OPD for problems other than Hepatitis and most of them presented with vague complaints like generalised body aches, tiredness and dyspeptic symptoms. They were randomly tested for Hepatitis C virus (HCV) antibodies by Immunochromatographic kit method. Positive samples for Hepatitis C antibodies were confirmed by third generation ELISA. Those who were confirmed were assessed for the risk factors associated with HCV transmission. RESULTS: The study included 9,564 patients. Out of them 4,230 (44.22%) were males and 5,334 (55.77%) were females. A total of 611 (6.38%) cases were positive for HCV; 257 (6.08%) were males, and 354 (6.64%) were females. Highest frequency (36%) was found between 21 and 30 years of age, and 60.54% positive patients were 21-40 years old. Blood transfusion was the most common (34.36%) risk factor followed by history of dental procedures (24.54%). In 27.16% no risk factor could be detected. CONCLUSION: Frequency of Hepatitis C is quite high in our population. Rate is higher in young adults. It is needed to adopt organised preventive strategies to overcome this problem. Blood transfusion is still the most significant risk factor followed by dental and surgical procedures. Health related procedures are still not safe in our set up and need to be addressed.

Management of facial gunshot wounds.

OBJECTIVE: To determine pattern and presentation in terms of site of injury, airway, associated injuries; and management of facial gunshot wounds. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Oral Surgery Department, Armed Forces Institute of Dentistry, Rawalpindi, between January 2001 and December 2008. METHODOLOGY: All patients with gunshot wounds of the face managed at the Oral Surgery Department during the study period were included by convenient sampling method. Patients were treated by a multidisciplinary team of maxillofacial surgeon, otorhinolaryngologist and plastic surgeon. Descriptive statistics were used to determine frequencies and mean + or - SD for qualitative and quantitative variables respectively. RESULTS: A total of 38 patients with gunshot wounds to the face were identified. Age ranged from 15 to 42 years with mean of 28 + or - 4.98 years. There were 32 (84%) males and 06 (16%) females. Twenty two (57%) patients required airway management. The most frequent site involved was mandible in 25 (65%) patients while midface was involved in 13 (35%) patients. Open reduction and internal fixation (ORIF) was performed in 17 (44%) patients, while 21 (56%) patients were managed conservatively. Out of 38 patients, 15 (39%) patients had some complications; trismus, sinusitis and infection being the most frequent (10.5% each). CONCLUSION: Facial gunshot wounds frequently involve mandible with more likely requirement of establishment of emergency airway and open reduction and internal fixation (ORIF). Early management of gunshot wounds results in better psychosocial profile, aesthetics, reduced hospital stay and early return to function.

Frequency of hepatitis B in asymptomatic patients of District Headquarter Hospital Kotli, Azad Kashmir.

BACKGROUND: Hepatitis B is prevalent throughout the world including Pakistan. A large proportion of patients suffering from Hepatitis B may be asymptomatic and can transmit the disease to healthy population. Objectives of this study were to estimate the frequency of Hepatitis B in asymptomatic adult population coming to District Headquarter Hospital Kotli, Azad Kashmir and to determine the risk factors associated with its transmission. METHODS: This was a cross-sectional study extending from January to December 2008. Subjects were randomly selected from those who attended the medial OPD of DHQ Hospital Kotli, Azad Kashmir for non-Hepatitis related problems. Both males and females between the ages of 15-80 years were included in the study. Blood samples taken from selected subjects were analysed for Hepatitis B surface antigen (HBsAg) by Immunochromatographic kit methods (ICT). Hepatitis B positive samples were further confirmed by third generation ELIZA. The patients thus confirmed were interrogated for different risk factors associated with transmission of Hepatitis B. RESULTS: A total of 9,564 patients were analysed. Out of them 4230 (44.22%) were males and 5334 (55.77%) were females. Overall 141 (1.47%) patients were positive for HBSAg, 71 (1.68%) males and 70 (1.31%) females. Patients between 21-30 years of age were most commonly effected (35.46%, n = 50). Blood transfusion was the most common risk factor (24.82%, n = 35) associated with Hepatitis B transmission followed by dental procedures (14.18%, n = 20). CONCLUSION: Frequency of Hepatitis B in asymptomatic people in this study was quite high. Blood transfusions and dental procedures were the most common risk factors associated with the transmission of Hepatitis B.