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Home > Molecular Characterization of Rare Genodermatoses in Pakistani Families.

Molecular Characterization of Rare Genodermatoses in Pakistani Families.

Thesis Info

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Author

Khan, Fehmida Farid

Program

PhD

Institute

Quaid-I-Azam University

City

Islamabad

Province

Islamabad.

Country

Pakistan

Thesis Completing Year

2020

Thesis Completion Status

Completed

Subject

Biotechnology

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/14386/1/Fehmida%20Farid%20Khan_Biotech_2020_QAU_PRR.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726690181

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Genodermatoses include a large group of inherited dermatological disorders that is often present with multisystem involvement resulting in various clinical manifestations due to genetic heterogeneity with pathogenic variations in more than 500 genes. Most genodermatoses occur early, during the neonatal period, infancy or early childhood, some conditions may appear later in life during adolescence or adulthood. Diagnosis of genodermatoses has been a major challenge and requires both clinical and investigational correlation to reach a diagnosis. Sometimes, even with comprehensive investigations, a definitive diagnosis cannot be achieved. With the arrival of new investigational. methods such as next generation sequencing, which not only successfully identified the molecular basis of many genodermatoses but also play important role in clinical use to help in the diagnosis of patients with suspected genodermatoses. In the current study, whole exome sequencing and Sanger sequencing were used to investigate genetic defects of nine Pakistani families affected with pseudoxanthoma elasticum (Families: A and B) and epidermolysis bullosa (Families: C,D E,F,G,H,I). Whole exome sequencing identified a novel homozygous frameshift variant (c.1799_1805dupGTCTGGT; p. Thr603fs*11) in ABCC6 in family A, a compound heterozygous variant (c.2294G>A; p.Arg765Gln and c.2974G>A; p.Gly992Arg) in ABCC6 in family B, a single nucleotide insertion variant (c.151insG; p.Gln226fs*) in LAMA3 in family C, two novel missense variants c.1285G>T (p.Asp429Tyr) and c.3373G>A (p.Gly1125Ser) in ITGB4 in family D, a novel homozygous missense variant c.1828A>G (p.Arg610Gly) in PLEC in family E, a heterozygous missense variant c.6209G>A (p.Gly2070Glu) in COL7A1 in family F, a homozygous frameshift variant c.676dupC (p.Gln226fs) in FERMT1 in family G, a homozygous nonsense variant c. C1705T in LAMB3 in family H and a homozygous nonsense variant c.C1573T (p.R525X) in COL7A1 in family I. In conclusion, two families affected with pseudoxanthoma elasticum and seven families affected with epidermolysis bullosa were identified with novel variants in ABCC6, ITGB4, and PLEC1. It should be assistive in the genetic counseling and prenatal diagnosis of the families as well as for the designing of improved diagnostic and therapeutic approaches.
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سید امجدؔ حسین حیدرآبادی

سید احمد حسین امجدؔ حیدرآبادی
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Role of Gender Variances in Job Satisfaction of Employee Working in Public Sector Universities

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Uterine Fibroid Embolization for Symptomatic Fibroids; Correlation of Mid-Term Changes in Disease-Specific Symptoms and Magnetic Resonance Imaging Results at a Teaching Hospital in Kenya

Background: Uterine fibroid embolization, though a widely available option in high income countries in managing symptomatic fibroids is relatively new in the East African region. It is currently offered at only one tertiary facility for the past three years. The symptom and radiological response in these patients, who literature suggests may have bigger fibroid burden and worse symptoms, is the subject of this study. Objective: Characterization of MRI imaging features in women undergoing uterine fibroid embolization and identification of clinical correlates in an African population. Methods: Patients with symptomatic fibroids who are selected to undergo UFE at the hospital formed the study population. The baseline MRI features, baseline symptom score, short term imaging outcome and mid-term symptom scores were analysed for interval changes. Assessment of potential associations between short term imaging features and the mid-term symptom scores were also done. Results: UFE resulted in statistically significant reductions (P< 0.001) of dominant fibroid and uterine volumes and in symptom severity scores of 43.7%, 40.1% and 37.8% respectively. Strong enhancement at baseline was a strong predictor of response to UFE.59% of respondents had more than ten fibroids. The predominant location of the dominant fibroid was intramural. No statistically significant association was found between clinical and radiological outcome. Discussion: UFE is a new treatment option for treatment of uterine fibroids in Kenya. This study was aimed at assessing outcomes to this treatment option compared to other parts of the world. The response of uterine fibroids to embolization in the African population is good but not different from findings reported in other studies in the West. The presence of multiple and large fibroids seen here is consistent with the case mix described in studies of African-American populations. No significant association is seen between radiological and clinical outcomes to UFE. Conclusion: UFE treatment for fibroids has good outcome. Further studies lasting beyond one year are indicated for further detailed outcome in the local African population. Recommendations: Patient counselling should emphasise the independence of volume reduction and symptom improvement. Volume changes are of relevance for the Radiologist in aiding understanding of the evolution of the condition and identifying potential technical treatment failures but should not be the main basis of evaluation of treatment success.