DEPDC5 mutations in familial and sporadic focal epilepsy.

BACKGROUND AND AIMS: Mutations in the disheveled, Egl-10 and pleckstrin domain-containing protein 5 (DEPDC5) gene have emerged as an important cause of various familial focal epilepsy syndromes. However, the significance of DEPDC5 mutations in patients with sporadic focal epilepsy has yet to be characterized. MATERIALS AND METHODS: We studied a kindred of familial focal epilepsy with variable foci using whole-exome sequencing. We subsequently studied a cohort of 293 patients with focal epilepsy and sequenced all exons of DEPDC5 using targeted resequencing. RESULTS: We reported a Taiwanese family with a novel splice site mutation which affected mRNA splicing and activated the downstream mammalian target of rapamycin (mTOR) pathway. Among patients with focal epilepsies, the majority (220/293) of these patients had sporadic focal epilepsy without malformation of cortical development. Two (0.9%) of these patients had probably pathogenic mutations in the DEPDC5 gene. DISCUSSION AND CONCLUSIONS: Our finding suggests that DEPDC5 is not only the most common gene for familial focal epilepsy but also could be a significant gene for sporadic focal epilepsy. Since focal epilepsies account for more than 60% of all epilepsies, the effect of mTORC1 inhibitor on patients with focal epilepsy due to DEPDC5 mutations will be an important future direction of research.

Association of HLA-B*15:13 and HLA-B*15:02 with phenytoin-induced severe cutaneous adverse reactions in a Malay population.

Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although HLA-B*15:02 is associated with PHT-induced SJS/TEN (PHT-SJS/TEN) in Han Chinese and Thais, the genetic basis for susceptibility to PHT-induced SCARs (PHT-SCAR) in other populations remains unclear. We performed a case-control association study by genotyping the human leukocyte antigen (HLA)-B alleles of 16 Malay PHT-SCAR patients (13 SJS/TEN and 3 DRESS), 32 PHT-tolerant controls and 300 healthy ethnicity-matched controls. A novel genetic biomarker, HLA-B*15:13, showed significant association with PHT-SJS/TEN (53.8%, 7/13 cases) (odds ratio (OR) 11.28, P=0.003) and PHT-DRESS (100%, 3/3 cases) (OR 59.00, P=0.003) when compared with PHT-tolerant controls (9.4%, 3/32 controls). We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls. These alleles may serve as markers to predict PHT-SCAR in Malays.

Staphylococcus Aureus Antibiotic Resistance In Atopic Eczema

Background: Atopic Dermatitis (AD) is a chronic relapsing, pruritic inflammation of the skin which is often colonized by Staphylococcus aureus. Antibiotic resistance of S. aureus is a constant challenge for clinicians who manages atopic dermatitis. Aim: To determine S. aureus antibiotic resistance pattern among patients with non-infected atopic dermatitis and its association with disease severity. Methods: One hundred and seventy eight participants (89 AD patients and 89 controls) were recruited from Universiti Malaya Medical Centre (UMMC). Participants were subjected to a questionnaire on demographics, personal and family medical conditions as well as antibiotic administration. AD severity were determined using Scoring Atopic Dermatitis (SCORAD). Skin swab was taken from eczematous lesion in patients and from left forearm in controls. Antibiotic susceptibility towards methicillin, vancomycin, rifampicin, fusidic acid, erythromycin, gentamicin, clindamycin, sulphamethoxazole, cefuroxime and penicillin were determined using disk diffusion method. Results for antibiotic resistance were categorized as none, sensitive and resistant. Results: Colonization of S. aureus in AD were significantly higher than control (p<0.001). Highest antibiotic resistance was reported for Penicillin (32/39, 82.1%), followed by Fusidic Acid (7/39, 17.9%) as well as Clindamycin and Erythromycin (3/39, 7.7% respectively). Two AD patient (5.1%) were resistant to Gentamicin. In addition, 1 AD patient (2.6%) was resistant towards Methicillin, Sulfamethoxazole and Cefuroxime respectively. No antibiotic resistance was reported for Vancomycin and Rifampicin among the AD patients. Conclusion: High resistance were found for Penicillin and Fusidic acid. Their usage and prescription should be reduced to preserve its sensitivity.

Cross-reactivity in AED-induced severe cutaneous adverse reaction: a case report

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A 7-Year Retrospective Review of Skin Cancer at University Malaya Medical Centre:A Tertiary Centre Experience

Introduction Skin cancer is ranked the ninth commonest cancer among males and tenth among females in Malaysia. Objectives To review the pattern of skin cancers at University Malaya Medical Centre (UMMC). Methods This is a retrospective review of all histo-pathological confirmed skin cancers at UMMC from 2004 till 2010. Results Among the 155 patients reviewed, basal cell carcinoma (BCC) was the commonest skin cancer (44.5%), followed by squamous cell carcinoma (SCC) (27.1%) and malignant melanoma (MM) (11.6%). The nodulo-ulcerative subtype made up 46% of all BCC while 50% of MM was of acral lentiginous subtype. Patients with BCC were significantly older (>60 years old), (p=0.003). A majority of skin cancers were found on the head and neck. Conclusion BCC was the commonest skin cancer, with significantly older patients and located mainly on head and neck. MM was the least common skin cancer but associated with the highest mortality.

A 7 years retrospective review of skin cancers: A University Malaya medical experience

Background: Skin cancer is ranked the ninth commonest cancer among male and tenth among female in Malaysia. Objective: To determine the pattern of skin cancers and demography of skin cancer sufferers in University Malaya Medical Centre (UMMC). Methods: This is a retrospective review of all histo-pathologically confirmed skin cancers in UMMC from 2004 to 2010. Patients with incomplete or missing data were excluded. Results: A total of 155 patient records were reviewed. The commonest skin cancer was basal cell carcinoma (BCC) (44.5%), followed by squamous cell carcinoma (SCC) (27.1%) and malignant melanoma (MM) (11.6%). The other skin cancers included dermatofibrosarcoma protuberans and cutaneous lymphoma (5.2% each), extramammary Paget’s disease 3.2% and Kaposi sarcoma 2.6%. A majority (78%) of BCC was of nodulo-ulcerative subtype while 50% of MM was of acral lentiginous melanoma subtype. BCC had a significantly higher number of patients from the older age group (>60 years old) compared to other skin cancers (p=0.003). SCC had significantly more male patients than other skin cancers (p=0.006). With the exception of MM, a majority of skin cancers were found on the head and neck. Conclusions: BCC was the commonest skin cancer followed by SCC and MM. Patients with BCC were older with a female preponderance and mainly located on the head and neck. MM was the least common of the three major skin cancers, but has the highest risk of metastasis and mortality.

Meperidine-induced serotonin syndrome in a susceptible patient.

We present a patient with a history of clomipramine-induced serotonin syndrome 5 yr prior who developed serotonin syndrome after a single dose of meperidine. This report heightens appreciation of population at risk and also recognition of potential toxicity in meperidine.