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.
Pain Insensitivity, Congenital

STUDY DESIGN: Cross sectional and observational. PURPOSE: To evaluate the different aspects of lumbar disc degenerative disc disease and relate them with magnetic resonance image (MRI) findings and symptoms. OVERVIEW OF LITERATURE: Lumbar disc degenerative disease has now been proven as the most common cause of low back pain throughout the world. It may present as disc herniation, lumbar spinal stenosis, facet joint arthropathy or any combination. Presenting symptoms of lumbar disc degeneration are lower back pain and sciatica which may be aggravated by standing, walking, bending, straining and coughing. METHODS: This study was conducted from January 2012 to June 2012. Study was conducted on the diagnosed patients of lumbar disc degeneration. Diagnostic criteria were based upon abnormal findings in MRI. Patients with prior back surgery, spine fractures, sacroiliac arthritis, metabolic bone disease, spinal infection, rheumatoid arthritis, active malignancy, and pregnancy were excluded. RESULTS: During the targeted months, 163 patients of lumbar disc degeneration with mean age of 43.92+/-11.76 years, came into Neurosurgery department. Disc degeneration was most commonly present at the level of L4/L5 105 (64.4%).Commonest types of disc degeneration were disc herniation 109 (66.9%) and lumbar spinal stenosis 37 (22.7%). Spondylolisthesis was commonly present at L5/S1 10 (6.1%) and associated mostly with lumbar spinal stenosis 7 (18.9%). CONCLUSIONS: Results reported the frequent occurrence of lumbar disc degenerative disease in advance age. Research efforts should endeavor to reduce risk factors and improve the quality of life.
Arthritis ; Arthritis, Rheumatoid ; Bone Diseases, Metabolic ; Humans ; Intervertebral Disc Degeneration* ; Low Back Pain ; Magnetic Resonance Imaging ; Neurosurgery ; Polymethacrylic Acids ; Pregnancy ; Quality of Life ; Risk Factors ; Sciatica ; Spinal Stenosis ; Spine ; Spondylolisthesis ; Walking ; Zygapophyseal Joint

Animals ; Brain ; embryology ; Ear ; embryology ; Esophagus ; embryology ; Fallopian Tubes ; embryology ; Female ; Heart ; embryology ; Humans ; Kidney ; embryology ; Liver ; embryology ; Lung ; embryology ; Male ; Organogenesis ; physiology ; Penis ; embryology ; Rabbits ; Stomach ; embryology ; Vagina ; embryology