Discovery of a novel and a rare Kristen rat sarcoma viral oncogene homolog (KRAS) gene mutation in colorectal cancer patients.

Colorectal cancer (CRC) is one of the most important causes of morbidity and mortality in the developed world and is gradually more frequent in the developing world including Saudi Arabia. According to the Saudi Cancer Registry report 2015, CRC is the most common cancer in men (14.9%) and the second most prevalent cancer. Oncogenic mutations in the KRAS gene play a central role in tumorigenesis and are mutated in 30-40% of all CRC patients. To explore the prevalence of KRAS gene mutations in the Saudi population, we collected 80 CRC tumor tissues and sequenced the KRAS gene using automated sequencing technologies. The chromatograms presented mutations in 26 patients (32.5%) in four different codons, that is, 12, 13, 17, and 31. Most of the mutations were identified in codon 12 in 16 patients (61.5% of all mutations). We identified a novel mutation c.51 G>A in codon 17, where serine was substituted by arginine (S17R) in four patients. We also identified a very rare mutation, c.91 G>A, in which glutamic acid was replaced by lysine (E31K) in three patients. In conclusion, our findings further the knowledge about KRAS mutations in different ethnic groups is indispensable to fully understand their role in the development and progression of CRC.

Extracurricular leadership development programme to prepare future Saudi physicians as leaders.

OBJECTIVE: To describe and evaluate an innovative approach for developing leadership skills in a cohort of medical students through an extracurricular programme. METHODS: The study was conducted at King Abdulaziz University, Jeddah, Saudi Arabia, from April to June of the academic year 2014-15, and comprised medical students from all batches. Mixed-method design was used to evaluate the leadership development programme. Pre- and post-tests were conducted to assess students' learning and their satisfaction was evaluated at the end of the programme. Focus groups were conducted to assess the programme's impact on participants' behaviour. Data analysis was done using SPSS 16. RESULTS: Of the 55 participants, 45(82%) responded to the evaluation survey. Of them, 29(65%) reported intended changes in their leadership practices immediately after the programme, with 8(28%) of them reporting more than one change. The mean students' satisfaction with the overall performance of the speakers and programme organisation was high at 4.12±0.91 and 4.54±0.89, respectively. CONCLUSIONS: Early experience of the leadership development programme produced positive results. An intense programme analysis is required to fully understand this significant organisational need.

Identification of a novel SBF2 missense mutation associated with a rare case of thrombocytopenia using whole-exome sequencing.

We describe in this report a case of a 6-years-old female who presented at the age of 1 month with a mucocutaneous bleeding and suspected thrombocytopenia. The patient's condition was refractory to the known idiopathic thrombocytopenic purpura treatments and congenital form of Thrombocytopenia was suspected following the delivery of a male sibling with the same phenotype. The patient also manifested fair colored hair and skin relative to her family however she did not have any detectable neurologic or other immunologic abnormalities. In order to further understand this condition, we have used whole-exome sequencing of the patient's DNA as well as her father's with the assumption that her condition is transmitted in an autosomal recessive manner. We have identified a missense change c.659C>G (p.Thr220Arg) in the SBF2 (also known as MTMR13) gene that causes a mutation in the DENN domain of the protein. This mutation was validated by traditional Sanger sequencing and analyzed in the remaining family members were it was found to segregate in the homozygous state in the affected siblings and in the heterozygous state in both parents. This novel mutation in the DENN domain of SBF2 maybe interfering with its putative association with the Rab family of small GTPases which are important mediators of vesicle transport and membrane trafficking. In conclusion, we have identified a novel mutation that is associated with severe thrombocytopenia. The fact that this mutation is found in SBF2 gene may indicate that the underlying cause of thrombocytopenia in our patient is either a new variant form of Griscelli syndrome (through the Rab GTPases action) or a variant Charcot-Marie-Tooth type 4 disease as SBF2 truncating mutations were previously identified in sufferers of this disease. This finding will help to accurately diagnose and classify similar cases of congenital thrombocytopenia and provide further proof to the power of whole-exome sequencing in personalizing patients management from the point of diagnosis to treatment and followup.