Publications by authors named "Naila Shaikh"

6 Publications

  • Page 1 of 1

Genetic Testing of Non-familial Deaf Patients for CIB2 and GJB2 Mutations: Phenotype and Genetic Counselling.

Biochem Genet 2017 Dec 31;55(5-6):410-420. Epub 2017 Oct 31.

Molecular Biology and Genetics Department, Medical Research Center, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan.

CIB2 and GJB2 genes variants contribute significantly in familial cases of prelingual recessive hearing loss (HL). This study was aimed to determine the CIB2 and GJB2 variants and associated phenotype in 150 non-familial individuals with HL. After getting informed consent, 150 non-familial deaf patients were enrolled and blood samples were obtained for DNA extraction. Pure tone air conduction audiometry was performed. Coding exons of CIB2 and GJB2 genes were Sanger sequenced. A tetra primer ARMS assay was developed for recurrent CIB2 variant. Four bi-allelic GJB2 variants, c.71G>A p.(Trp24*), c.231G>A p.(Trp77*), c.235delC p.(Leu79Cysfs3*) and c.35delG p.(Gly11Leufs24*), were found in nine hearing impaired individuals. We also found four homozygotes and five carriers of c.380G>A p. (Arg127His) variant of controversial clinical significance. CIB2 sequencing revealed single recurrent variant c.272T>C p. (Phe91Ser) segregating with HL in ten individuals. Among our patients, c.71G>A (p.Trp24*) was the most common variant, accounted for 45% of GJB2 variants. Two known GJB2 variants, c.235delC p. (Leu79Cysfs3*) and c.310del14 p. (Lys105Argfs2*), are reported here for the first time in Pakistani population. Our data further support the benign nature of c.380G>A p. (Arg127His) variant. For CIB2, c.272T>C p. (Phe91Ser) is the second common cause of HL among our sporadic cases. Phenotypically, in our patients, individuals homozygous for GJB2 variants had profound HL, whereas CIB2 homozygotes had severe to profound prelingual HL. Our results suggest that GJB2 and CIB2 are common cause of HL in different Pakistani ethnicities.
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http://dx.doi.org/10.1007/s10528-017-9828-3DOI Listing
December 2017

IL28B rs12980275 polymorphism shows association with response to treatment in Pakistani patients with chronic hepatitis C.

J Med Virol 2015 May 4;87(5):814-20. Epub 2015 Feb 4.

Molecular Biology and Genetics Department, Medical Research Center, Liaquat University of Medical and Health Sciences, Jamshoro; Department of Pathology, Liaquat University of Medical and Health Sciences, Jamshoro.

The aim of this study was to describe the genetic characteristics of Pakistani patients infected with hepatitis C virus (HCV) in relation to IL28B polymorphisms and its association to interferon and ribavirin treatment response. A total of 220 patients, infected with HCV were enrolled, out of which 100 were responders and 120 were nonresponders. The whole blood samples were collected to extract viral RNA and genomic DNA. PCR following the restriction fragment length polymorphism method was used to genotype IL28B rs12979860, rs8099917, and rs12980275 polymorphisms. Liver biopsies and HCV genotyping were performed in nonresponder patients. The rs12980275 AA genotype exhibited significant correlation to treatment response and was found in 62% of the responders and 37.5% of nonresponder patients, whereas AG genotype was noticed frequently in the nonresponder group (P < 0.0001). The rs12979860 CT and rs8099917 TT genotypes were found in 74% and 66% of the responders as compared to 58.3% and 50.8% in nonresponder patients (P = 0.001 and P = 0.032) respectively. HCV 3a genotypes were detected in 50.8% of the nonresponder patients. No significant association was detected between liver biopsy findings and IL28B SNPs (P > 0.05). The results showed the significant association of rs12980275 polymorphism with treatment response in HCV patients followed by rs12979860 and rs8099917. This is the first report describing the association of rs12980275 with response to HCV treatment from Pakistan. These findings may help in predicting the outcome of pegylated interferon and ribavirin treatment in HCV patients, and may reduce the side effects and cost of treatment in predicting non-responder patients.
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http://dx.doi.org/10.1002/jmv.24100DOI Listing
May 2015

Mutational spectrum of the CYP1B1 gene in Pakistani patients with primary congenital glaucoma: novel variants and genotype-phenotype correlations.

Mol Vis 2014 7;20:991-1001. Epub 2014 Jul 7.

Molecular Biology and Genetics Department, Medical Research Center, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan ; Department of Pathology, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan.

Purpose: This study aimed to investigate the role of CYP1B1 mutations in primary congenital glaucoma (PCG) in Pakistani patients.

Methods: After consent was received, 20 families with at least more than one member affected with primary congenital glaucoma were enrolled in the study. The disease was confirmed with standard ophthalmological investigations. Genomic DNA was extracted from whole blood for localization of linkage and sequencing. Bioinformatics tools were used to assess the predicted pathological role of novel variants.

Results: Ten out of 20 families (50%, 10/20) showed homozygosity with CYP1B1-linked short tandem repeat (STR) markers. On direct sequencing of the CYP1B1 gene in the linked families, six mutations, including two novel pathogenic variants, were identified. p. R390H was the most frequently found mutation in five families (50%, 5/10), whereas c.868_869insC, p.E229K, and p.A115P were found once in three families. Two novel mutations, a missense mutation (p.G36D) and an in-frame deletion mutation (p.G67-A70del), were segregated with disease phenotype in two families. Age of disease onset was congenital in all mutations; however, disease severity and response to clinical interventions varied among the mutations and families. Haplotype analysis using five polymorphisms revealed a distinct haplotype for a common mutation.

Conclusions: This is the largest cohort of Pakistani patients with PCG to be genetically screened for CYP1B1 mutations. Identifying common mutation and genotype-phenotype correlations may help in genetic testing and better prognosis for the disease. Novel mutations identified in the study may help in better understanding the pathophysiology of CYP1B1-associated glaucoma.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087121PMC
September 2014

Frequency and pattern of retinopathy in newly diagnosed type 2 diabetic patients at tertiary care settings in Abbottabad.

J Ayub Med Coll Abbottabad 2012 Apr-Jun;24(2):87-9

Linquat University of Medical and Health Sciences Jamshoro, Pakistan.

Background: Retinopathy is one of the most frequent and serious complication of diabetes mellitus and leading cause of blindness worldwide. The objective of this study was to determine frequency and pattern of retinopathy in newly diagnosed type 2 diabetic patients at tertiary care settings in Abbottabad.

Methods: This was a descriptive cross-sectional comparative study being conducted at Ayub Teaching Hospital and Northern Institute of Medical Sciences Abbottabad. It included 100 newly diagnosed type 2 diabetic patients who were attending diabetic clinics of these tertiary care hospitals. Already diagnosed type 2 patients taking anti-diabetic medication, type 1 diabetes mellitus, hypertension, retinal vasculitis, retinal vessel occlusion, and sickle cell retinopathy were excluded. After pupillary dilatation, detailed fundoscopic examination was carried out via direct ophthalmoscopy and further confirmed by an ophthalmologist. According to fundoscopic findings, retinopathy was graded into background, pre-proliferative and proliferative types.

Results: Total 100 patients were included, with mean age 45.1 +/- 3.2 years, 60% of them were females. Overall, 17% of type 2 diabetic patients had retinopathy within one month of diagnosis. Background retinopathy was predominant (12%) followed by pre-proliferative (4%) and proliferative (1%) lesions.

Conclusion: Frequency of retinopathy in newly diagnosed type 2 diabetic patients seems to be higher than previous reports and background lesions were predominant. Detailed fundoscopic examination of all newly type 2 diabetic patients at the time of diagnosis is of paramount importance.
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February 2014

Study for frequency and aetiology of lymphadenopathy during combination therapy for chronic hepatitis C (pegylated interferon alpha plus ribavirin) at a tertiary care hospital in Hyderabad.

J Pak Med Assoc 2011 Oct;61(10):986-9

Department of Medicine, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan.

Objectives: To find out the frequency and etiology of lymphadenopathy at various sites distant from perihepatic region during combination therapy (pegylated interferon Alpha Plus Ribavirin) for chronic hepatitis C.

Methods: Retrospective case-control study conducted at Medical unit I of Liaquat University Hospital Jamshoro, Sind, Pakistan. The charts of 205 patients undergoing antiviral therapy with pegylated interferon alpha plus ribavirin for chronic hepatitis C at our ward from May 2009 to April 2010, were reviewed for those who developed lymphadenopathy at sites distant from perihepatic region.

Results: Out of 205 patients, 130 (63.41%) were males. Mean age of males was 37.11 +/- 9.81 years and of females 42.31 +/- 8.79 years. In total, 20 (9.75%) patients in control or 10/95 (10.52%) patients treated within clinical trials, were recorded to have lymphadenopathy during combination antiviral therapy for chronic hepatitis C. The most common site of lymphadenopathy was inguinal region in 08 (40%), followed by cervical region in 07 (35%) patients. Majority 16 (80%) of patients having lymphadenopathy were infected with HCV genotype 3a, and 17 (85%) have achieved sustained virological response. The etiology of lymphadenopathy was reactive in most 15 (75%) of our patients, followed by tuberculosis in 03 (15%). The average time for onset of lymphadenopathy during antiviral therapy for chronic hepatitis C was 21 weeks.

Conclusion: In conclusion, lymphadenopathy at various sites distant from perihepatic region appears to be higher than that documented in previous studies. In majority of our patients, the lymphadenopathy was reactive and resolved upon cessation of antiviral therapy.
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October 2011

Study of snake bite cases at Liaquat University Hospital Hyderabad/Jamshoro.

J Ayub Med Coll Abbottabad 2008 Jul-Sep;20(3):125-7

Department of Medicine, Liaquat University of Medical and Health Sciences Jamshoro, Pakistan.

Background: Envenoming resulting from snakebites is an important public health hazard in many regions. It is common in rural areas not to delay access to life saving anti-venom. The objectives of this study were to know about common types of snakes in local areas, clinical features in snakebite victims, complications in snakebite case, and mortality rate in snakebite victims in rural Sindh.

Methods: This descriptive study was conducted at 4 medical wards of Liaquat University Hospital Hyderabad/Jamshoro, Sindh from 1st January 2006 to December 2006. One hundred cases with history of snakebite were analysed. Both genders were included in study. Patients with history of trauma, insect bite or thorn prick were excluded from the study. Clotting time (CT) was the main bedside procedure, to assess the degree of envenomation.

Results: One hundred (100) cases from both genders, from 8 to 55 years age were reviewed. There were 57 (95%) viper bites (haemotoxic) having haemostatic abnormalities and 3 (5%) elapid (neurotoxic) bites presented with neuroparalytic symptoms. Most cases were from Tando Mohammad Khan and Hyderabad (rural) districts of Sindh. All viotims had localized oedema at the site of bite. Fang/teeth marks were noted in (90%) cases. Majority (80%) were bitten on the legs below knee. Some 40% of the cases of snakebite occurred when the patient was asleep. Urban to rural ratio was 1:4.5 and male to female ratio was 4:1. Mean time to arrival at our hospital after the bite was 3 hours and mean duration of hospital stay was 4 days. One patient had acute renal failure (ARF) and disseminated intravascular coagulation (DIC), 3% cases of elapid bites were shifted to ICU for assisted ventilation, 4 patients (5.5%) had adverse effects after anti-venom administration and needed intravenous hydrocortisone, promethazine and subcutaneous adrenaline. The average dose of anti-venom was 60 vials for viper bites and 10 vials for elapid bites. Overall mortality rate was 4%.

Conclusions: Snakebites are common in the rural population of developing countries. There is need to educate the public about the hazards of snake bite, early hospital referral and treatment.
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August 2009