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 oracle study - fibromyalgia, prevalence and severity in the hospital setting in the Pakistani population.

OBJECTIVE: To assess the prevalence and severity of fibromyalgia in hospital-visiting patients. METHODS: The cross-sectional study was conducted at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from July, 2018, to January, 2019, and comprised patients aged 18-75 years of either gender. Demographic information, comorbidities and previous medications were recorded for each patient. The modified American College of Rheumatology preliminary diagnostic criteria 2010-11 for fibromyalgia diagnosis. If diagnosed, the fibromyalgia impact questionnaire was administered to assess its severity. Data was analysed using SPSS 25. RESULTS: Of the 750 hospital-visiting patients, fibromyalgia was diagnosed in 250(33.3%); 190(76%) of them being females (p<0.0001). Comorbidities, age and increased elevated body mass index were significantly associated with fibromyalgia. Severity was not influenced by comorbidities, marital status, education or economic status (p>0.05). Menarche at a later age and menstrual irregularity were associated with fibromyalgia severity (p<0.05). CONCLUSIONS: The hospital-based prevalence of fibromyalgia was found to be high, especially among females.

A cross sectional study to assess nasal carriage of methicillin resistant Staphylococcus aureus in healthcare professionals in a tertiary care hospital.

OBJECTIVE: To determine the nasal carriage of staphylococcus aureus and methicillin-resistant staphylococcus aureus among healthcare workers in a tertiary care setting. METHODS: The cross-sectional study was conducted at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from April to July 2018, and comprised healthcare workers at the institution. Nasal swabs were collected and cultured on Mannitol salt agar. Mannitol fermenting colonies which were gram-positive cocci, catalase-positive and coagulase-positive were identified as staphylococcus aureus. Antibiotic susceptibility test was performed by modified Kirby-Bauer disc diffusion method. Methicillin resistance was detected using cefoxitin disc diffusion method. Data was analysed using SPSS 23. RESULTS: Of the 210 nasal swabs, 52(24.76%) had a staphylococcus aureus growth, and of them, 15(7.1%) were methicillin-resistant. No association could be established with either any single category of healthcare worker or an inter-department variation (p>0.05). Likewise, there was no association with age, gender, duration of service, smoking, co-morbidities, use of antibiotics in the preceding six months, treating a patient with methicillin-resistant staphylococcus aureus in the preceding six months and hospitalisation in the preceding year (p>0.05). CONCLUSIONS: The frequency of nasal carriage of methicillin resistant staphylococcus aureus amongst healthcare workers was regardless of the nature of their professional engagement.