Zarina Abdul Latiff

Molecular Diagnosis of Severe Combined Immunodeficiency—Identification of IL2RG , JAK3 , IL7R , DCLRE1C , RAG1 , and RAG2 Mutations in a Cohort of Chinese and Southeast Asian Children

Severe combined immunodeficiencies (SCID) are a group of rare inherited disorders with profound defects in T cell and B cell immunity. From 2005 to 2010, our unit performed testing for IL2RG, JAK3, IL7R, RAG1, RAG2, DCLRE1C, LIG4, AK2, and ZAP70 mutations in 42 Chinese and Southeast Asian infants with SCID adopting a candidate gene approach, based on patient’s gender, immune phenotype, and inheritance pattern. Mutations were identified in 26 patients, including IL2RG (n = 19), IL7R (n = 2), JAK3 (n = 2), RAG1 (n = 1), RAG2 (n = 1), and DCLRE1C (n = 1). Among 12 patients who underwent hematopoietic stem cell transplantation, eight patients survived. Complications and morbidities during transplant period were significant, especially disseminated bacillus Calmette–Guérin disease which was often difficult to control. This is the first cohort study on SCID in the Chinese and Southeast Asian population, based on a multi-centered collaborative research network. The foremost issue is service provision for early detection, diagnosis, management, and definitive treatment for patients with SCID. National management guidelines for SCID should be established, and research into an efficient platform for genetic diagnosis is needed.

Vincristine-induced vocal cord palsy: case report and review of the literature.

Vincristine-induced vocal cord paralysis is a rare but serious complication. We report 2 patients with acute lymphoblastic leukemia who developed progressive stridor during induction chemotherapy. There were no clinical features of peripheral or autonomic neuropathy. Flexible laryngoscopy confirmed the diagnosis of bilateral vocal cord palsy; interestingly, the nerve conduction test revealed axonal motor neuropathy involving the median and common peroneal nerves in both patients. The first patient required prolonged ventilatory support necessitating unilateral cordectomy before extubation, whereas the second only required supplemental oxygen therapy. There was resolution of stridor in the first patient after cordectomy and gradual clinical improvement in the second. These cases illustrate that a high index of suspicion of vincristine-induced vocal cord palsy with prompt otolaryngology consultation for laryngoscopy is required in the diagnostic evaluation of a patient who has received vincristine.

The first Malay database toward the ethnic-specific target molecular variation

BackgroundThe Malaysian Node of the Human Variome Project (MyHVP) is one of the eighteen official Human Variome Project (HVP) country-specific nodes. Since its inception in 9th October 2010, MyHVP has attracted the significant number of Malaysian clinicians and researchers to participate and contribute their data to this project. MyHVP also act as the center of coordination for genotypic and phenotypic variation studies of the Malaysian population. A specialized database was developed to store and manage the data based on genetic variations which also associated with health and disease of Malaysian ethnic groups. This ethnic-specific database is called the Malaysian Node of the Human Variome Project database (MyHVPDb).FindingsCurrently, MyHVPDb provides only information about the genetic variations and mutations found in the Malays. In the near future, it will expand for the other Malaysian ethnics as well. The data sets are specified based on diseases or genetic mutation types which have three main subcategories: Single Nucleotide Polymorphism (SNP), Copy Number Variation (CNV) followed by the mutations which code for the common diseases among Malaysians. MyHVPDb has been open to the local researchers, academicians and students through the registration at the portal of MyHVP (http://hvpmalaysia.kk.usm.my/mhgvc/index.php?id=register).ConclusionsThis database would be useful for clinicians and researchers who are interested in doing a study on genomics population and genetic diseases in order to obtain up-to-date and accurate information regarding the population-specific variations and also useful for those in countries with similar ethnic background.

Family History of Early Infant Death Correlates with Earlier Age at Diagnosis But Not Shorter Time to Diagnosis for Severe Combined Immunodeficiency

Background Severe combined immunodeficiency (SCID) is fatal unless treated with hematopoietic stem cell transplant. Delay in diagnosis is common without newborn screening. Family history of infant death due to infection or known SCID (FH) has been associated with earlier diagnosis. Objective The aim of this study was to identify the clinical features that affect age at diagnosis (AD) and time to the diagnosis of SCID. Methods From 2005 to 2016, 147 SCID patients were referred to the Asian Primary Immunodeficiency Network. Patients with genetic diagnosis, age at presentation (AP), and AD were selected for study. Results A total of 88 different SCID gene mutations were identified in 94 patients, including 49 IL2RG mutations, 12 RAG1 mutations, 8 RAG2 mutations, 7 JAK3 mutations, 4 DCLRE1C mutations, 4 IL7R mutations, 2 RFXANK mutations, and 2 ADA mutations. A total of 29 mutations were previously unreported. Eighty-three of the 94 patients fulfilled the selection criteria. Their median AD was 4 months, and the time to diagnosis was 2 months. The commonest SCID was X-linked (n = 57). A total of 29 patients had a positive FH. Candidiasis (n = 27) and bacillus Calmette–Guérin (BCG) vaccine infection (n = 19) were the commonest infections. The median age for candidiasis and BCG infection documented were 3 months and 4 months, respectively. The median absolute lymphocyte count (ALC) was 1.05 × 109/L with over 88% patients below 3 × 109/L. Positive FH was associated with earlier AP by 1 month (p = 0.002) and diagnosis by 2 months (p = 0.008), but not shorter time to diagnosis (p = 0.494). Candidiasis was associated with later AD by 2 months (p = 0.008) and longer time to diagnosis by 0.55 months (p = 0.003). BCG infections were not associated with age or time to diagnosis. Conclusion FH was useful to aid earlier diagnosis but was overlooked by clinicians and not by parents. Similarly, typical clinical features of SCID were not recognized by clinicians to shorten the time to diagnosis. We suggest that lymphocyte subset should be performed for any infant with one or more of the following four clinical features: FH, candidiasis, BCG infections, and ALC below 3 × 109/L.

External squeeze test during pediatric laparoscopic hernia repair: a novel on-table assessment to ensure complete closure of patent processus vaginalis

php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Open Access Surgery 2018:11 1–3 Open Access Surgery Dovepress

Genotype-phenotype correlation among Malaysian patients with osteogenesis imperfecta

BACKGROUND Osteogenesis imperfecta (OI) is a rare genetic bone disease characterized by bone fragility and low bone mass. OI was mainly caused by genetic mutations in collagen genes, COL1A1 and COL1A2. Nevertheless, new genes have been identified to be causally linked to OI. The clinical features between each OI groups share great similarities and it is sometimes difficult for clinicians to diagnose the disease accurately. Here, we identify the genetic mutations of OI patients from Malaysia and correlate the genetic mutations with the clinical features. METHOD Targeted sequencing of fourteen genes panel was performed to identify the mutations in 29 OI patients with type I, III, IV and V disease. The mutations were determined using Ion Torrent Suite software version 5 and variant annotation was conducted using ANNOVAR. The identified mutations were confirmed using Sanger sequencing and in silico analysis was performed to evaluate the effects of the candidate mutations at protein level. RESULTS Majority of patients had mutations in collagen genes, 48% (n = 14) in COL1A1 and 14% (n = 4) in COL1A2. Type I OI was caused by quantitative mutations in COL1A1 whereas most of type III and IV were due to qualitative mutations in both of the collagen genes. Those with quantitative mutations had milder clinical severity compared to qualitative mutations in terms of dentinogenesis imperfecta (DI), bone deformity and the ability to walk with aid. Furthermore, a few patients (28%, n = 8) had mutations in IFITM5, BMP1, P3H1 and SERPINF1. CONCLUSION Majority of our OI patients have mutations in collagen genes, similar to other OI populations worldwide. Genotype-phenotype analysis revealed that qualitative mutations had more severe clinical characteristics compared to quantitative mutations. It is crucial to identify the causative mutations and the clinical severity of OI patients may be predicted based on the types of mutations.

Anorectal anomaly with rectovestibular fistula: a historical comparison of neonatal anterior sagittal anorectoplasty without covering colostomy and postoperative anal dilatation to the classical three-stage posterior sagittal anorectoplasty

php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Open Access Surgery 2017:10 33–44 Open Access Surgery Dovepress

The role of delayed laparoscopic suction for intra-abdominal collection or abscess post appendectomy in paediatric patients: case series and review of literature

1Paediatric Surgery Unit, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Jalan Yaacob Latiff, Cheras, Kuala Lumpur 56000, Malaysia. 2Department of Anaesthesia, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Jalan Yaacob Latiff, Cheras, Kuala Lumpur 56000, Malaysia. 3Department of Radiology, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Jalan Yaacob Latiff, Cheras, Kuala Lumpur 56000, Malaysia. 4Department of Paediatrics, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Jalan Yaacob Latiff, Cheras, Kuala Lumpur 56000, Malaysia.

How many meals should you skip before undergoing a colonoscopy? A randomized controlled trial: association between duration of abstinence from solid food to cleanliness of the bowel in patients undergoing elective colonoscopy

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Open Access Surgery 2015:8 9–20 Open Access Surgery Dovepress

Iatrogenic Abdominal Wall Defect from Chronic Evisceration of Intestine: AComplication of Fetal Vesicoamniotic Shunt

Vesico-amniotic shunt is one of the methods used to relieve fetal bladder obstruction in some cases of lower urinary tract obstruction. We highlight a 35 week gestation baby boy, who developed acquired abdominal wall defect following placement of the antenatal vesico-amniotic shunt. It is one of the rare complications of placement of vesico- amniotic shunt.