Analysis of RAB27A Gene in Griscelli Syndrome type 2: Novel Mutations Including a Deletion Hotspot

INTRODUCTION: Griscelli syndrome type 2 is an autosomal recessive disorder characterized by pigmentary dilution and occurrence of acute phases of hemophagocytosis. The disease is caused by mutations in RAB27A gene, coding a small GTPase involved in terminal phases of cytotoxic granule/melanosome exocytosis. MATERIALS AND METHODS: We describe the result of mutation analysis among nine patients from seven non-related Persian families. We present four novel mutations including a deletion hot spot (514del 5). CONCLUSION: This hot spot is flanked by "direct repeats" of nucleotides, which are previously shown to be associated with areas of recurrent small deletions.     

Severe combined immunodeficiency: A cohort of 40 patients

Severe Combined Immunodeficiency (SCID) consists of a heterogeneous group of genetic disorders characterized by an arrest in T lymphocyte development which is variably associated with an abnormal differentiation of B and NK cells. In order to depict the clinical state of Iranian patients with SCID, records of forty patients were reviewed. Patients were classified based on the flow cytometry data in two groups of B− and B+. In thirty two families (80%) parents were consanguine and in 17 families (50%) there were affected members other than proband. We showed that autosomal forms of SCID might be more frequent due to higher rate of consanguineous marriages. Alongside several infective complications, complicated Bacillus Calmette-Guérin (BCG) vaccination was documented in 18 cases (45%) following the routine vaccination at birth. BCG immunization is still a part of standard vaccination for newborns in developing countries; whereas in communities with a better health condition it could be held for a few months and performed for kids whose immune system sounds intact. We discuss where consanguine mating is common, a test of screening should be run timely. A complete blood count of cord blood could reveal lymphocytopenia at birth; this helps early diagnosis. Genetic consultation would help the families with affected members preventing new SCID offspring.     

The effect of oral evening primrose oil on menopausal hot flashes: a randomized clinical trial

Purpose

Hot flashes are common experience for menopausal women, and for many, are severe enough to significantly compromise their overall sense of well being and quality of life. The aim of this study was to compare the efficacy of evening primrose with placebo in improvement of menopausal hot flashes.

Methods

In a 6-week randomized clinical trial, a total of 56 menopausal women aged 45–59 years were participated in this study. The patients were asked for their hot flashes characteristics and responded to HFRDIS (hot flash related daily interference scale) questionnaire before and after the intervention. The participants were randomly assigned to take two capsules per day (totally 90 capsules for 6 weeks) of placebo or evening primrose (500 mg) for continuous 6 weeks. Then, the improvement in hot flashes was compared between two groups.

Results

The percent of improvement in hot flash frequency, severity and duration were 39, 42 and 19 %, in evening primrose group compared with 32, 32 and 18 % in placebo group, respectively. Although all three characters of hot flash was ameliorated in evening primrose arm, only its severity was significantly better in this arm compared with placebo group (P < 0.05). All HFRDIS score were significantly improved in two groups, but the percentage of improvement in social activities, relations with others, and sexuality was significantly superior to placebo group (P < 0.05).

Conclusions

The application of oral evening primrose oil compared with placebo for controlling hot flashes may decrease more the intensity of attacks as well as ameliorating the HFRDIS score.     

Frequency of Genotype With ΔF508 Mutation in CFTR Gene Among Iranian Cystic Fibrosis Patients With Pancreatic Insufficiency

Background:

Cystic fibrosis (CF) is the most prevalent lethal autosomal recessive disease with a broad spectrum of phenotypes. Mutation of ΔF508 in the CFTR gene is the most important and lethal mutation in CF, which contains 70% of all predisposing mutations for CF worldwide.

Objectives:

Determining frequency of genotypes with ΔF508 mutation in CFTR gene, and evaluation of correlation between genotype and phenotype of Iranian patients with CF.

Patients and Methods:

Thirty six patients were included in this cross sectional study. ΔF508 mutations in both alleles of the CFTR gene were checked.

Results:

Among 36 pediatric patients, ΔF508 mutation was detected in 9 (25%) patients; 2 patients were heterozygous, and 7 patients homozygous for this mutation. From overall 72 tracked alleles, 11 (15.2%) were found to have ΔF508 mutations. Differences in prevalence of dyspnea and bronchiectasis were significant in homozygote group, compared with non-mutated group for ΔF508.

Conclusions:

It seems that more ΔF508 mutated alleles lead to more severe symptoms of CF.     

Self-management programs conducted within a practice setting: Who participates,who benefits and what can be learned?

Objective

To investigate the impact of generic and diabetes-specific self-management programs offered in a real world context.

Methods

A quasi-experimental design with 12-week follow-up compared Living with a Chronic Condition and Living with Diabetes. Self-report data collected included: Self-management Knowledge and Skills; Health Related Quality of Life (HRQOL); Depression; Social Isolation; Loneliness; Self-efficacy; and Health Behaviours.

Results

Participants (N = 458) in the two programs differed on almost all baseline measures. Both demonstrated statistically significant improvements in Self-management Knowledge and Skills, as well as reductions in depression. In addition to younger age, low HRQOL, high self-efficacy and Positive and Active Engagement in Life, were the clinical factors most likely to lead to improvements in HRQOL and self-efficacy. Changes in different characteristics predicted different outcomes.

Conclusion

Both generic and disease-specific programs led to improved outcomes, despite the two programs attracting significantly different participants. Referral patterns also differed but GP referral rates were low for both.

Practice implications

Positive participant outcomes can be achieved in real life clinical settings. While younger people with a positive attitude may appear to gain more, it is important to encourage people from low socio-economic status to enter these programs so that social inequalities in health are not worsened.     

Variation in plasma leptin levels in young Iranian children with cystic fibrosis

Introduction

Poor weight gain is one of the most important mortality hazards in cystic fibrosis (CF) patients. The mechanisms that may hinder body weight regulation are not completely understood. Leptin and its role in fat mass could be related to control of weight gain in CF patients. As the previous data are conflicting, we aimed to investigate serum leptin level in Iranian CF children compared to a control group.

Material and methods

Forty-three CF patients aged from 3 to 120 months and 43 age-matched controls were enrolled. Patients were recruited from the outpatient clinic of the Children''s Medical Center Hospital. Controls were visited in the general outpatient clinic for an annual check-up. Both groups were divided into three subgroups based on age: 3 to 12 months, 13 to 48 months, and 49 to 120 months. Body mass index (BMI) was calculated for all the participants. Serum leptin levels were measured applying a solid phase enzyme-linked immunosorbent assay (ELISA).

Results

Leptin levels and BMI values were significantly different between patients and controls (p = 0.02, p < 0.001, respectively) but only patients aged 13–48 months had significantly higher levels of leptin than age-matched controls (p = 0.016). Overall male patients’ mean leptin level was significantly higher than in female patients (p = 0.032) and male controls (p < 0.001).

Conclusions

Leptin level in our patients was significantly higher than controls. It seems that leptin levels during infancy are higher than in adult patients. Further studies are required on specific genotypes, gender and age to reveal the probable correlation with BMI and leptin levels in CF patients from different ethnic groups.     

The results of allogenic cancellous bone graft in medial opening wedge high tibial osteotomy

European Journal of Orthopaedic Surgery & Traumatology - There is no clear consensus regarding the optimal filling agent in the medial opening wedge high tibial osteotomy (MOWHTO). In this...     

Adaptation and implementation of family-based treatment enhanced with dialectical behavior therapy skills for anorexia nervosa in community-based specialist clinics

Although family-based therapy (FBT) is a well-established treatment for anorexia nervosa, its implementation and effectiveness in clinical settings has been neglected. A group of seven therapists at a community-based eating disorders clinic were trained in skills-enhanced FBT and provided treatment to 11 youth with anorexia nervosa. Family-based skills training, which borrowed heavily from dialectical behavior therapy, was introduced in four additional sessions and then integrated throughout the remainder of FBT. FBT was perceived as appropriate and acceptable by all participants. Therapists reported high treatment fidelity. There was a large improvement in weight and moderate improvement in caregiver-reported eating disorder psychopathology but no clinically significant change by youth report. This study provides preliminary data on the implementation and effectiveness of FBT in the community.     

BCGiosis as a presenting feature of a child with chronic granulomatous disease

Bacillus Calmette Guerin (BCG) vaccine, which is administered to all newborns in some regions, could lead to serious complication ranging from local disease (known as BCGitis) to disseminated disease (BCGosis) in a group of patients with primary immunodeficiency diseases. We are reporting here a 3.5 year-old girl with a history of prolonged BCGitis, which developed to disseminated disease without any other special features. Immunological studies with nitro-blue tetrazolium test confirmed the diagnosis of chronic granulomatous disease in this patient. Chronic granulomatous disease should be considered in the list of differential diagnosis in all children with BCGosis, even in the absence of any other manifestations related to immunodeficiency.     

Genetic and molecular findings of 38 Iranian patients with chronic granulomatous disease caused by p47‐phox defect

One of the components of NADPH oxidase is p47‐phox, encoded by NCF1 gene. This study aims to find new genetic changes and clinical features in 38 Iranian patients with autosomal recessive chronic granulomatous disease (AR‐CGD) caused by NCF1 gene defect. Patients who had abnormal NBT and DHR‐1,2,3 assay with loss of p47‐phox in Western blotting were included in this study. After recording demographic and clinical data, PCR amplification was performed followed by direct sequencing for all exons and exon‐intron boundaries. The most common form of CGD in Iran was AR‐CGD due to consanguinity marriages. Among patients with AR‐CGD, NCF1 deficiency was found to be more common than other forms. Cutaneous involvements (53%), pulmonary infections (50%) and lymphadenopathy (29%) were more prevalent than other clinical manifestations of CGD. Mutation analysis of NCF1 gene identified five different mutations. Homozygous delta GT deletion (c.75_76delGT) was the most frequent mutation and was detected in more than 63% of families. Six families had a nonsense mutation in exon 7 (c.579G > A). Two novel mutations were found in exon 4 in two families, including a missense mutation (c.328C > T) and a nine‐nucleotide deletion (c.331_339delTGTCCCCAC). Genetic detection of these mutations may result in early diagnosis and prevention of possible complications of the disease. This could be useful for timely decision‐making for haematopoietic stem cell transplantation and for carrier detection as well as prenatal diagnosis of next children in the affected families. Our findings might help to predict outcomes, raise awareness and help effective treatment in these patients.