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Home > Molecular Characterization of Autosomal Recessive Congenital Ichthyosis

Molecular Characterization of Autosomal Recessive Congenital Ichthyosis

Thesis Info

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Author

Karim, Noreen

Program

PhD

Institute

Quaid-I-Azam University

City

Islamabad

Province

Islamabad.

Country

Pakistan

Thesis Completing Year

2019

Thesis Completion Status

Completed

Subject

Medical Genetics

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/10354/1/Noreen%20Karim_Med%20Genetics_2019_QAU_PRR.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726681986

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Autosomal recessive congenital ichthyosis (ARCI) is a genetically and phenotypically heterogeneous group of non-syndromic cornification disorders characterized primarily by generalized hyperkeratotic epidermal scales with or without erythroderma. So far, pathogenic variants in fourteen genes have been associated with ARCI most of which perturb lipid metabolism and localization during cornification, thereby disrupting the lipid envelope and thus barrier function. Research is in progress to reduce or treat the disease manifestations in affected individuals by enzyme replacement therapy and gene therapy. Moreover, gene expression studies and histopathological studies have been performed to discover more effective drug targets. However, a more precise genotype to phenotype correlation and a greater understanding of the pathophysiology would aid in developing more specific therapies. Therefore, the necessity is to elucidate the link between a defective gene and the resulting difference in expression of proteins in epidermis. In the current study whole exome sequencing (WES), Sanger sequencing and mass spectrometry were used to investigate four consanguineous Pakistani families (A, B, C, and D) affected with ARCI. WES identified a frameshift mutation c.364dupA (p.T122IfsX3) in SDR9C7 in family A, a nonsense mutation c.762C>G (p.Tyr254*) in PNPLA1 in family B, a missense mutation c.944G>A (p.R315H) in TGM1 in family C, and a missense mutation c.424 (p.R142C) in TGM1 in family D. Mass spectrometry of purified proteins isolated from epidermal corneocytes samples of the affected individuals confirmed the deleterious effects of the identified mutations. Combinatorial protein analysis of the three groups (PNPLA1, SDR9C7, and TGM1) identified common 20 proteins with altered expression in all the disease groups indicating their central role in ARCI pathology. Furthermore, a proteomic spectrum specific for each type of ARCI was also acquired. In conclusion, four families affected with ARCI were identified with mutations in SDR9C7, PNPLA1, and TGM1 along with the proteomic profiles that could aid in the genetic counseling and prenatal diagnosis of the families as well as devising improved diagnostic and therapeutic approaches for ARCI.
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حاجی عبدالرحمن

حاجی عبدالرحمن
شذرات لکھے جاچکے تھے کہ راقم (ضیاء الدین اصلاحی) کے والد حاجی عبدالرحمن صاحب وفات پاگئے۔ اناﷲ وانا الیہ راجعون۔ ۱۱؍ نومبر کو جمعہ کی نماز کے بعد تجہیز و تکفین ہوئی۔ قارئین معارف سے دعائے مغفرت کی درخواست ہے۔
(ضیاء الدین اصلاحی، نومبر ۱۹۹۴ء)

آلودہ پانی کی مروجہ تحلیل و تطہیر کا سائنسی و شرعی جائزہ

Water symbolizes life on the earth. All kinds of existence depend on water. Allah has created great reservoirs of water on this earth which cater to the needs of all living beings, but human negligence is making these resources polluted. Pollution not only poses threats to human life, it also endangers marine life and resources. These threats have been increased manifold by industrial revolution and increasing human population. The same factors are also responsible for the increased use of water. Many countries have employed distillation processes to provide clean water for the increasing demands of population, agriculture and industries. Islamic jurisprudence also takes into account different types of water, some of which can be used in cleansing rituals for worship, while some cannot be used. The question arises whether the purified water by scientific process will be "Ṭahir & Muṭṭahir" and can be used for ablution and other Islamic rituals? Will Islamic Jurist accept it as "Istiḥalah"? The following study will outline the details of distilled water to see whether it can be used for daily chores and ablution rituals or not.

Family of Numerical Methods for the Solutions of Two Point Boundary-Value Problems Using Non-Polynomial Spline Functions

The research presented in this dissertation is aimed at the development of family of numerical solutions of Two Point Boundary-Value Problems (BVP) in all the branches of engineering sciences with higher precision. In such engineering related boundary-value problems the boundary conditions are specified at two points. The core of this dissertation is focused on the development of a new technique based on quartic non-polynomial spline functions, connecting spline functions values at "mid knots" for the numerical approximations to engineering BVPs and their corresponding values of the fourth-order derivatives. This new approach, which is recently being cited, is so developed that it leads to a family of numerical methods that may be used for computing approximations to the solution of a system of boundary-value problems of third and fourth-order associated with contact and sandwich beam problems. This research work is furthered on the development of a family of higher order numerical solutions to special non-linear third-order boundary-value problems. It is shown that the developed family of higher order methods gives better approximations in contrast to the existing numerical methods. It has further been shown that the existing second, fourth- order and higher order finite-difference and spline functions based methods become special cases of our new technique developed at mid knots presented in this dissertation. Results from the numerical experimentation of renowned problems are also given to illustrate applicability and efficiency of the newly developed family of numerical methods.