|
Document Type |
: |
Thesis |
|
Document Title |
: |
GENETIC OF CONGENITAL SKIN DISORDERS IN SAUDI FAMILIES الاضطرابات الجلدية الوراثية في المملكة العربية السعودية |
|
Subject |
: |
Faculty of medicine |
|
Document Language |
: |
Arabic |
|
Abstract |
: |
Genetics of Congenital Skin Disorders in Saudi Families By: Sami Raja Alallasi, Supervisor: Dr. Noor A. Shaik Congenital skin disorders refer to the inherited cutaneous abnormalities, which are present in patients at birth. Epidermolysis Bullosa (EB) and Congenital Ichthyosis (CI) are two common examples of congenital skin conditions which have become the prototypes of emerging developments in molecular genetics of genodermatoses In this study, we have enrolled two families, one with Epidermolysis Bullosa and one with Congenital Ichthyosis based on their clinical diagnosis, disease history, and family pedigree. Each participant (father, mother, index case and the affected sibling) of the enrolled families have provided venous blood samples in EDTA tubes. In family A, where the index case suffering with Lamellar ichthyosis the disease was identified to be caused by novel compound heterozygous mutations (c.1141G>A and c.758-1G>C) in Transglutaminase-1 gene (TGM1), which were inherited from parents. Our computational analysis has predicted that p.Ala381Pro variant causes several structural disturbances in Transglutaminase-1(Tgase-1) protein, by altering its conformation, stability, solvent accessibility and hydrogen bonding properties. The c.758-1G>C variant could abrogate the normal AG acceptor site at exon -intron junction and leads to the retainment of intron- 4 retention and produce long mRNA, which would eventually undergo non-sense mediated mRNA decay. Both TGM1 mutations could have caused lower levels of transglutaminase activity in skin and caused the Lamellar ichthyosis. In family B with Epidermolysis Bullosa, the index was seen to have inherited the c.915G>A mutation from both parents in an autosomal recessive mode. The c.915G>A mutation causes the premature truncation of protein at 305th amino acid, which is 167 amino acids shorter than the actual 472 amino acid long protein. The premature truncation of KRT14 protein at 305th amino acid residue . |
|
Supervisor |
: |
Dr. Noor A. Shaik |
|
Thesis Type |
: |
Master Thesis |
|
Publishing Year |
: |
1443 AH
2022 AD |
|
Added Date |
: |
Saturday, March 19, 2022 |
|
Researchers
| سامي رجاء العلاسي | Alallasi, Sami Raja | Researcher | Master | |
|