Homozygous mutations in NTRK1 gene underlie congenital insensitivity to pain with anhidrosis in Pakistani families

Congenital insensitivity to pain with anhidrosis is a rare autosomal recessive disorder presenting with loss of pain sensation, thermal sensation defects, and self-mutilating behavior. In the present study, we recruited two consanguineous pedigree showing pain insensitivity symptoms from Pakistan for clinical and molecular investigations. In family A, one female patient displayed classical CIPA symptoms along with microcephaly and severe intellectual disability. During course of the disease, her right foot was amputated and had remarkable dental degeneration and teeth shedding. In family B, one boy presented with classical symptoms of congenital insensitivity to pain with anhidrosis. Blood was collected from both families for molecular studies. Sequencing with the Ilumina Trusight One Sequencing Panel covering 4813 OMIM genes revealed a known homozygous mutation c.2084C>T; p.P695L of NTRK1 in family A and a novel truncated mutation c.2025C>G; p.Y681X in family B. Protein modeling analysis of both mutations (p.P695L and p.Y681X) predicted loss of the rigidity in tyrosine kinase domain of NTRK1 that led to conformational changes as well as deleterious effect on protein function. The known mutation was reported more than a decade ago in a family from Northern Israel and other non-sense mutation is newly identified. It is interested that most of NTRK1 mutations are associated with this domain. This is first ever report of NTRK1 variants in congenital insensitivity to pain with anhidrosis patients from Pakistan.

Adult mortality in medical, sociodemographic and healthcare perspective

Statistics on causes of deaths can help in determining the pattern and burden of disease and devise measures for planning and controlling unwanted deaths. To assess the pattern of mortality in adult patients in a public sector tertiary care hospital at Rawalpindi during the year 2005. This retrospective study was done through search of hospital records of all deaths in adults during the year 2005 in a public sector tertiary care hospital. Information on pertinent variables was obtained on a proforma. Cause of death in each case was ascertained as it was documented. Important Lab. Investigations, where available were also recorded. Diseases were grouped according to World Health Organization classification [International Classification of Diseases-10]. Causes deaths were analyzed under various medical, sociodemographic and healthcare parameters according to available records. A total of 529 adult deaths occurred during study period. The mean age of the deceased was 54 years. There were 58% males with 13% being unmarried. More than 75% cases belonged to lower socioeconomic status while 55% belonged to urban areas. Almost all [97%] were admitted through casualty department. Hospital stay was less than one hour in 34% and 1-7 days in 52% cases. Death due to diseases of circulatory system was ranked first [33%]. A total of sixty deaths occurred due to liver diseases and hepatitis C virus was positive in 39 [64%] cases. Proportion of female who died of hypertensive disorders was significantly high [p < 0.01]. Both infectious and non infectious diseases are bringing a major death toll in our health setting with circulatory system and liver disease as the leading causes of death in adults. Adult mortality can be reduced by controlling infectious and non infectious diseases