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Document Type |
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Thesis |
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Document Title |
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Molecular Diagnosis of Rare Single Gene Disorders in Families from The South-Western Region of Saudi Arabia التشخيص الجزيئي لأمراض أحادية الجين نادرة في أسر من المنطقة الجنوب غربية من المملكة العربية السعودية |
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Subject |
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Faculty of Medicine |
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Document Language |
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Arabic |
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Abstract |
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Saudi Arabia is one of the highly inbred populations of the world. Socioeconomic, geographic, cultural and traditional isolation of human populations leads to ethnic groups specificities. Single gene or Mendelian disorders although rare in general populations but become more frequent in highly inbred populations such as Saudi Arabia, which leads them to appear in a homozygous condition. Previously genome wide homozygosity mapping followed by candidate gene sequencing has been used for causative variants identification but since the advent of whole exome sequencing (WES), gene identification has been revolutionized in genetic diagnosis of rare disorders in Saudi Arabia.
This study presents four families (A-D), collected from the South-Western region of the Kingdom. Clinical and molecular investigations of these families was performed in the department of Genetic Medicine, King Abdulaziz University, Jeddah.
Family A was diagnosed as Wolcott-Rallison syndrome, and Sanger sequencing analysis revealed a novel variant in the EIF2AK3 gene (c.1764-2A>G). Family B was diagnosed as non-Herlitz type of junctional epidermolysis bullosa (NH-JEB), and WES followed by Sanger sequencing revealed two novel variants in LAMB3 gene causing NH-JEB phenotype in family B (c.1977-1G>A, and c.484C>T). The results of these two families were published in international journals. On the other hand, Family C had clinical symptoms of congenital microphthalmia and family D had congenital intellectual disability; however, were not labelled with any known or specific clinical diagnosis. Genome-wide homozygosity mapping through SNP-microarray followed by WES analysis failed to identify the causative variants in these families.
The study concludes that clear clinical diagnosis aids in successful genetic diagnosis. WES analysis might have deficiencies by not covering all the coding genes or the universal WES kits may not be specific for the Saudi Arabian population. Thus, whole genome re-sequencing is recommended for those samples in which WES analysis. |
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Supervisor |
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Dr. Musharraf Jelani |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1440 AH
2019 AD |
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Co-Supervisor |
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Prof. Jumana Al-Aama |
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Added Date |
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Tuesday, January 22, 2019 |
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Researchers
| همس سعيد الزهراني | Alzahrani, Hams Saeed | Researcher | Master | |
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