oa Neuromuscular Disorders: Clinical, Genomic and Proteomic Databases

Building clinical and genetic databases for inherited muscle diseases in Qatar was one of our aims for the PPM1 grant that we were awarded. Through this QNRF-funded research grant, 267 subjects were enrolled: 222 subjects were recruited and 45 patients’ data were collected from the medical records of HMC-Cerner system. Of the 267 subjects, 127 were patients and 140 were unaffected family members. All recruitments were at HMC-site. Clinical data collection and data entry for NMDs patients have been completed for 124 of the 127 patients (3 patients removed from the clinical database due to a confirmed genetic diagnosis of a central disease associated with muscle weakness rather than primary muscular diseases). The 124 patients were derived from 104 families of 18 different ethnicities. The percent distributions of three main ethnic groups were 54% Qatari patients, 28% Arab (non-Qatari) and 18% as non-Arab. The Arab non-Qatari families involved 10 ethnicities and the non-Arab families involved 7 ethnicities. The ethnic origin of the 104 families was distributed over 6 subcontinents; 69% were West Asian, 13% South Asian, 11% North African, 4% sub-saharan African, 2% southeast Asian, and 1% Western European. We categorized the NMDs in our patients’ cohort into 9 main clinical groups with the congenital muscular dystrophy, CMD, as the most prevalent group. The genetic analysis of 118 NMDs patients, applying whole genome sequencing, has successfully identified the disease-causing genes in 95 patients. The causative genes have remained yet unidentified in 23 patients. The concluded detection rate in our cohort was 81%. Two founder recessively inherited mutations, in LAMA2 and SCGA genes were identified in Qatari patients. Details of the distribution of mutated genes and variants’ inheritance/ classification will be presented. Applying the Aptamer-based Somalogic large scale proteomic screening, our study identified 58 of 1317 protein markers significantly altered in patients as compared to the healthy control. 73 of 1317 markers were significantly altered in a selected subgroup of patients that had LAMA2 related congenital muscular dystrophy. There were 32 proteins in common between all cases and the subgroup. Of these 32 common proteins, 21 markers have been shown to replicate another published international study on Duchenne Muscular Dystrophy, which points to a high reliability of our results.