Point of Care Exome Sequencing Reveals Allelic and Phenotypic Heterogeneity Underlying Mendelian disease in Qatar.

The effectiveness of next generation sequencing at solving genetic disease has motivated the rapid adoption of this technology into clinical practice around the world. In this study, we use whole exome sequencing (WES) to assess 48 patients with Mendelian disease from 30 serial families as part of the "Qatar Mendelian Disease pilot program" - a coordinated multi-center effort to build capacity and clinical expertise in genetic medicine in Qatar. By enrolling whole families (parents plus available siblings), we demonstrate significantly improved discriminatory power for candidate variant identification over trios for both de novo and recessive inheritance patterns. For the same index cases, we further demonstrate that even in the absence of families, variant prioritization is improved up to 8-fold when a modest set of population-matched controls is used vs large public databases, stressing the poor representation of Middle Eastern alleles in presently available databases. Our in-house pipeline identified candidate disease variants in 27 of 30 families (90%), 23 of which (85%) harbor novel pathogenic variants in known disease genes, pointing to significant allelic heterogeneity and founder mutations underlying Mendelian disease in the Middle East. For 6 of these families, the clinical presentation was only partially explained by the candidate gene, suggesting phenotypic expansion of known syndromes. Our pilot study demonstrates the utility of WES for Middle Eastern populations, the dramatic improvement in variant prioritization conferred by enrolling population-matched controls and/or enrolling additional unaffected siblings at the point-of-care, and 25 novel disease-causing alleles, relevant to newborn and premarital screening panels in regional populations.

Azathioprine induced acute sialadenitis: A case report.

Key clinical message: Patients presenting with acute sialadenitis need careful review of their medications. Azathioprine is one of such drugs, which can rarely induce acute sialadenitis. Prompt discontinuation of the medication leads to reversal of the patient condition. Abstract: Acute sialadenitis is one of the rare adverse effects of azathioprine. We report a case of acute submandibular sialadenitis following initiation of azathioprine which resolved upon discontinuation of the drug.

Podocyte infolding glomerulopathy after 25 years of clinical remission of lupus nephritis in a patient with systemic lupus erythematosus: A case report and review of literature.

Podocyte infolding glomerulopathy (PIG) is a rare pathological finding that has gained more recognition recently. Most of the reported cases have been associated with connective tissue diseases especially systemic lupus erythematosus (SLE). Here we report the first case of Infolding Glomerulopathy associated with SLE in the Middle East.

Posterior Reversible Encephalopathy Syndrome (PRES) in Rheumatic Autoimmune Disease.

Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiological entity with many causes. The primary abnormality is cerebral vasogenic oedema. Here we describe the management of five patients with PRES syndrome who presented to our hospital. LEARNING POINTS: Posterior reversible encephalopathy syndrome (PRES) presents with cerebral vasogenic oedema.PRES resolves when blood pressure is controlled.Patients with a history of autoimmune disorder who present with confusion may have PRES.

Seronegative Bilateral Symmetrical Inflammatory Polyarthritis: Think Twice Before Starting Immunosuppression.

The most common cause of bilateral symmetrical polyarthritis in the small joints is rheumatoid arthritis. However, if seronegative arthritis is involved, it could be the case that other underlying causes need to be diagnosed. This is particularly important for those coming from or living in developing countries where infectious causes should always be considered. The case of a young Nepali woman is presented in this article. She was referred as a case of seronegative rheumatoid arthritis for DMARDs therapy but this was not the case due to her origin from Nepal and seronegativity for RF, Anti-ccp, and ANA as well as faint macular skin lesions over her face and upper extremities, which the patients are not aware of. Consequently, skin biopsy was carried out which subsequently confirmed that the infectious cause of her polyarthritis was leprosy. LEARNING POINTS: Bilateral symmetrical seronegative inflammatory arthritis of rheumatoid type is very common.However, when both RF and anti-ccp are negative, other possible secondary causes including infection should be considered, especially in patients from areas where disease is endemic.In this case lepromatous leprosy was the cause of the patient's presumed rheumatoid arthritis and all her arthritis resolved after her leprosy had been treated.

Vitamin D status in health care professionals in Qatar.

OBJECTIVE: To investigate the prevalence of vitamin D deficiency among health care professionals working at Hamad Medical Corporation in Doha, Qatar. METHODS: Between 15th January 2007 and 15th January 2008, 340 healthy volunteers were included in this study. Each subject completed a diary to determine the duration of sunlight exposure, and vitamin D supplements. Serum levels of 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), calcium, phosphorus, alkaline phosphatase, total protein, and albumin were obtained. Those with abnormal results were called for counselling. RESULTS: The mean overall vitamin D level was 11.7 ng/ml. It was lower in females (10.3 ng/ml) than in males (13.7 ng/ml). Ninety-seven percent of all participants had a mean level <30 ng/ml. Eighty-seven percent had a mean level of <20 ng/ml. CONCLUSION: We concluded that the prevalence of vitamin D deficiency among health care professionals in Qatar is very high.

Skeletal tuberculosis mimicking seronegative spondyloarthropathy.

Skeletal tuberculosis (TB) is still a common problem in developing countries. It is a postprimary manifestation of TB and appears usually with fever, pain, tenderness, and limitation of motion at the involved site. We present a patient with a clinical course very suggestive of seronegative spondyloarthropathy and who had partially responded to sulphasalazine (SSZ) and nonsteroidal anti-inflammatory drugs (NSAID) but proved later to be a TB case.