OBJECTIVES: To evaluate etiologic factors associated with spinal cord injury (SCI) severity and to identify predictive factors of reduction in SCI severity in six countries.
SETTING: SCI centers in Bangladesh, India, Malaysia, Nepal, Sri Lanka, and Thailand.
METHODS: Data from centers collected between October 2015 and February 2021 were analyzed using descriptive statistics and logistic regression.
RESULTS: Among 2634 individuals, the leading cause of SCIs was falls (n = 1410, 54%); most occurred from ≥1 meter (n = 1078). Most single-level neurological injuries occurred in the thoracic region (n = 977, 39%). Greater than half of SCIs (n = 1423, 54%) were graded American Spinal Injury Association Impairment Scale (AIS) A. Thoracic SCIs accounted for 53% (n = 757) of all one-level AIS A SCIs. The percentage of thoracic SCIs graded AIS A (78%) was significantly higher than high cervical (52%), low cervical (48%), lumbar (24%), and sacral (31%) SCIs (p
METHODS: Whole-exome sequencing (WES) was carried out on a 15-year-old male proband of Pakistani ancestry who had severe obesity. This was followed by family segregation analysis, using Sanger sequencing. We also undertook re-analysis of WES data from 91 unrelated adults with severe obesity (86% white European ancestry) from the Personalised Medicine for Morbid Obesity (PMMO) cohort, recruited from the UK National Health Service.
RESULTS: We identified an oligogenic mode of inheritance of obesity in the proband's family-this provided the impetus to reanalyze existing sequence data in a separate dataset. Analysis of PMMO participant data revealed two further patients who carried more than one rare, predicted-deleterious mutation in a known monogenic obesity gene. In all three cases, the genes involved had known autosomal dominant inheritance, with incomplete penetrance.
CONCLUSION: Oligogenic inheritance may explain some of the variable penetrance in Mendelian forms of obesity. We caution clinicians and researchers to avoid confining sequence analysis to individual genes and, in particular, not to stop looking when the first potentially-causative mutation is found.