Intragenic deletion mutation in the gene desmoglein 4 underlies autosomal recessive hypotrichosis in six consanguineous families

Objectives: Localized autosomal recessive hypotrichosis is a non-syndromic human hair loss disorder, affecting scalp, eyebrows and eyelashes, and other parts of the body. Six consanguineous families with this form of hair loss disorder were investigated at both the clinical and molecular levels

Methods: Linkage in six families with twenty-one affected members was tested by genotyping microsatellite markers linked to autosomal recessive hypotrichosis loci including localized autosomal recessive hypotrichosis [LAH] 1, 2 and 3. Sequence analysis of the entire coding and splice sites of the gene DSG4 was performed to search for the disease-causing mutation

Results: Genotyping established linkage in families to the DSG4 gene at LAH1 locus on chromosome 18q21.1. Sequence analysis detected an intragenic deletion mutation [Ex5_8 del] in affected members of all six families

Conclusion: Identification of recurrent mutation in six additional Pakistani families strengthens the body of evidence that this is an ancestral mutation that is widespread among different Pakistani ethnic groups

Comparative analysis of autosomal and x-linked genes involved in nonspecific cognitive impairment

The focus of research on candidate gene identification of recessive non-syndromic cognitive impairment is increasing and to date 19 genes for X-linked and 10 autosomal non-syndromic mental retardation have been reported. The X chromosome has higher proportion of cognitive genes as compared to autosomes; but the presence of 22 autosomes and the origination of X chromosome from autosome during the course of evolution is putting a mark of question on this fact and leads to the hypothesis that the number of autosomal cognitive genes should be higher in number than the genes on X chromosome. The comparative analysis of both sets [autosomal v/s X-linked] of genes revealed significant similarities with respect to their evolutionary conservation, cellular localization, molecular and biological functions, protein domain sharing, subcellular expression profiling in nervous tissues, etc. The results and observation conclude that the knowledge of X-linked cognitive genes can be utilized in a variety of ways to explore more autosomal cognitive genes computationally

Comparative efficacy of intravenous methylprednisolone versus intravenous hydrocortisone in acute severe asthma

To compare the efficacy of intravenous methylprednisolone versus intravenous hydrocortisone in acute severe asthma It was a quasi-experimental interventional study, conducted on 60 patients of acute severe asthma, presenting to the emergency department of MH Rawalpindi. Military Hospital Rawalpindi from Jan 2001 to Dec 2002. Patients fulfilling the criteria were divided into two groups of 30 patients each by convenience sampling. Group-I received intravenous methylprednisolone sodium succinate 125 mg as a single dose within half an hour of admission while group-2 received intravenous hydrocortisone 200 mg bolus followed by three doses of 100mg at six hours interval for next 24 hours. In addition, both the groups received nebulized salbutamol 2.5 mg diluted with 5 ml of distilled water at an interval of 30 minutes for first hour then 4 hourly along with oxygen at a rate 4-5 liters /minutes. Pulse rate and peak expiratory flow rate [PEFR: best of three attempts] were recorded on admission and subsequently at interval of six, twelve, eighteen and twenty-four hours of admission. Significant improvement in pulse rate was defined as its fall below 100 per minute and that of PEFR as its rise above 65% of predicted. Out of sixty patients, 41 were males and 19 were females. Their mean age was 38 years [range 19-50 years]. Significant improvements in pulse rate and PEFR were noted at interval of 24 hours in both groups, and this improvement was more marked in gropu-2. Target reduction [< 100/minute] in mean pulse rate was seen in 70% of patients in group-2 versus 26.7% in group-1. Target mean PEFR [> 65% of predicted] was achieved in 86.7% [group-2] and 40% [group-1]. The differences of mean pulse rate and PEFR at 24 hours were statistically significant. Intravenous hydrocortisone is more effective than intravenous methylprednisolone, at the dosages selected, in setting of acute severe asthma

Evaluation of AST/ALT ratio as a marker of liver fibrosis and cirrhosis in patients with chronic hepatitis C

To assess the relation between serum AST/ALT ratio [AAR] and hepatic fibrosis and cirrhosis associated with chronic hepatitis C. A cross sectional study. The study was conducted in the department of medicine Military Hospital Rawalpindi from Sep 2004 - Feb 2005. Fifty diagnosed patients of chronic hepatitis C were selected whose liver biopsy was performed as a workup plan fro treatment. Serum AST/ALT ratio [AAR] was determined and degree of liver fibrosis noted on histopathology, using Knodell scoring system. ANOVA was applied to study the difference in AAR in different stages of liver fibrosis. The mean AAR was found to be higher with each increasing stage of liver fibrosis. The mean AAR in cirrhotics [1.34] was significantly higher compared to noncirrhotics [0.77], p<0.001. AAR >/= 1 had 100% sensitivity and negative predictive value in distinguishing cirrhotic from non-cirrhotic patients with 87% specificity and 45% positive predictive value. There is only a modest relation between AAR and early hepatic fibrosis [stages 1-3] in patients with chronic hepatitis C, while AAR is significantly higher in patients with advanced fibrosis/ cirrhosis