A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1.

BACKGROUND: Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare hereditary disorder characterized by defects in teeth, hair, and nails in association with a fusion of the digits. Genetically, the disease phenotypes are caused by homozygous and compound heterozygous variants in NECTIN4 gene. OBJECTIVE: The main objective of the study was to identify the pathogenic sequence variant(s) for family screening and identification of carriers. METHODS: In the present study, the authors have investigated a large consanguineous family of Pakistani origin segregating autosomal recessive EDSS1. All the coding exons of the NECTIN4 gene were directly sequenced using gene-specific primers. RESULTS: The affected individuals presented the classical EDSS1 clinical features including sparse hair, hypoplastic nails with thick flat discolored nail plates, peg-shaped, conical, and widely spaced teeth with enamel hypoplasia, proximal cutaneous syndactyly of fingers and toes. Sequence analysis of the coding region of the NECTIN4 identified a novel nonsense variant [c.163C>T; p.(Arg55*)] in exon-2 of the gene. Computational analysis of protein structure revealed that the variant induced premature termination at Arg55 located in Ig-like V-loop region leading to loss of Ig-C2 type domains and transmembrane region, and most likely Nectin-4 function will be lost. STUDY LIMITATION: Gene expression studies are absent that would have strengthened the findings of computational analysis. CONCLUSION: The present study expanded the phenotypic and mutation spectrum of the NECTIN4 gene. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families.

A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1

Abstract Background Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare hereditary disorder characterized by defects in teeth, hair, and nails in association with a fusion of the digits. Genetically, the disease phenotypes are caused by homozygous and compound heterozygous variants in NECTIN4 gene. Objective The main objective of the study was to identify the pathogenic sequence variant(s) for family screening and identification of carriers. Methods In the present study, the authors have investigated a large consanguineous family of Pakistani origin segregating autosomal recessive EDSS1. All the coding exons of the NECTIN4 gene were directly sequenced using gene-specific primers. Results The affected individuals presented the classical EDSS1 clinical features including sparse hair, hypoplastic nails with thick flat discolored nail plates, peg-shaped, conical, and widely spaced teeth with enamel hypoplasia, proximal cutaneous syndactyly of fingers and toes. Sequence analysis of the coding region of the NECTIN4 identified a novel nonsense variant [c.163C>T; p.(Arg55*)] in exon-2 of the gene. Computational analysis of protein structure revealed that the variant induced premature termination at Arg55 located in Ig-like V-loop region leading to loss of Ig-C2 type domains and transmembrane region, and most likely Nectin-4 function will be lost. Study limitation Gene expression studies are absent that would have strengthened the findings of computational analysis. Conclusion The present study expanded the phenotypic and mutation spectrum of the NECTIN4 gene. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families.

The Use of Islamic Patterned Art Therapy: Healing of Psychological Problems Among University Students.

This study was designed to adopt art therapy from an Islamic perspective by adding/including shapes and designs of Islamic origin. This was basically color therapy and was designed to find its effectiveness in reducing depression, anxiety. Stress and enhancing psychological well-being of university students with high and low-religious levels from Islamabad and Rawalpindi. This study was carried out in two phases. The first phase was to develop Islamic adult coloring book with Islamic patterns and calligraphy. The second phase was the main study, and it was an experimental study which included screening out a sample, consisting of mild to moderate levels of depression, anxiety and stress and high and low-religiosity levels. A sample of 60 university students received Islamic patterned art therapy. On the basis of religiosity, two groups were formed as either a high-religious group or a low-religious group with individuals in both groups completing fourteen sessions. Pre- and post-test assessments were undertaken via the psychometric tools DASS-21, psychological well-being scale and religiosity scale. Statistics from the independent sample t-test and paired sample t-test and repeated measures ANOVA for within group and between group comparisons, revealed that there was a significant difference from pre-test to post-test assessments of depression anxiety and stress and psychological well-being, whereas there were nonsignificant gender differences on the bases of high and low-religiosity levels. Therefore, it could be concluded that Islamic patterned art therapy was found effective in reducing depression anxiety stress and increasing psychological well-being of university students.

EFFECT OF HORMONAL CONTRACEPTIVES ON SERUM SEROTONIN IN FEMALES OF REPRODUCTIVE AGE GROUP.

BACKGROUND: Many types of hormonal contraceptives are in use nowadays for example oral pills, emergency contraceptive pills, vaginal rings, implantable rods and injectable contraceptives (combined and progestogens only). The purpose of this study was to determine and compare serum serotonin levels in married fertile females of reproductive age group using hormonal contraceptives with non-contraceptive users. METHODS: A total of 300 women were selected in the study. This cross sectional study included three groups; Group-1 (control), group-2 (combined oral contraceptive users) and group-3 (injectable contraceptive users). History and examination of subjects were recorded on pro forma. Levels of serum serotonin were measured using standard ELISA kits. Results were analysed by one way ANOVA and a p-value 0.05% was taken as significant, using SPSS 16.0. RESULTS: The mean age of the patients in group-1 was 30.4 ± 6.1 years, group-2 was 28.9 ± 4.9 and in group-3 was 2.5 ± 6.8 years. For subjects in group-1, group-2 and group 3 the mean ± SD concentration of serum serotonin was 160.68 ± 53.27 ng/dl, 227.3 ± 63.98 ng/dl and 118.19 ± 31.32 ng/dl. A significant (p = 0.00) difference was seen among three groups, i.e., group-1, group-2 and group-3. After applying Post HOC Tukey's HSD, there was statistically no significant difference between group-1 and group-2 (p = 0.956). Difference was seen between group-2 and group-3 (p = 0.00), it was also significant between group-3 and group-1 (p = 0.00). CONCLUSION: It was concluded that hormonal contraceptives affect the levels of serum serotonin.

Insulin Sensitivity To Trace Metals (Chromium, Manganese) In Type 2 Diabetic Patients And Non Diabetic Individuals.

BACKGROUND: Diabetes mellitus constitutes one of the most important problems in developing and non-developing countries. The purpose of the study to estimate the concentrations of Chromium and Manganese in diabetic and non-diabetic population of Hazara division. The cross sectional comparative study was carried out on one hundred blood samples of Type 2 Diabetic patients collected non-randomly from Ayub Teaching Hospital and one hundred normal healthy controls from Women Medical College Abbottabad from September 2014 to April 2015. METHODS: The study included two hundred subjects. Among them 100 were diabetic and 100 non diabetic respectively. The blood samples were collected from Ayub Medical College, Abbottabad. The serum Chromium and Manganese levels were determined by Atomic Absorption spectrophotometer. RESULTS: Serum Chromium and Manganese levels were decreased in diabetic and increased in non-diabetic patients. CONCLUSIONS: Low serum level of Chromium and manganese were found in diabetic patients as compare to non-diabetic individuals.

EVALUATION OF TOXIC HEAVY METALS IN AYURVEDIC SYRUPS SOLD IN LOCAL MARKETS OF HAZARA, PAKISTAN.

BACKGROUND: Herbal and Ayurvedic preparations, widely used in Pakistan and the developing world, present serious risk of heavy metal toxicity related to their medicinal content and prolonged use by patients. The objective of this study was to find out the concentration of heavy metals in Herbal & Ayurvedic liquid preparations commonly used for treatment of different diseases, from local markets of Hazara. METHODS: The cross sectional survey of traditional herbal & Ayurvedic medicine shops included ten liquid preparations selected from local shops of Mansehra and Abbottabad after interviewing the shopkeepers; so as to select the most commonly sold preparations along with their indications. All samples were analysed on standard Atomic Absorption Spectroscopy for qualitative and quantitative study of toxic heavy metals (Mercury, Iron, Zinc, Lead, Manganese and Arsenic). RESULTS: Toxic levels of Mercury were present in seven syrups, i.e., (Kashneeze, Akseer e Pachas, Tankar, Sharbat e folad, Urosinal, Akseer e Jigar and Amrat dhara) while Arsenic was present only in Urosinal. Iron, Zinc, Manganese and Lead were present in permissible limits in all syrups. CONCLUSION: Mercury and Arsenic are present in local Herbal & Ayurvedic liquid preparations far beyond the permissible limits as proposed by the International Regulatory Authorities for health drugs while the rest of metals, i.e., Zinc, Manganese, and Iron are within the therapeutic limits.