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Title: Molecular genetic analysis of inherited kidney disease in Saudi Arabia
Authors: Al-Hamed, Mohamed Hashem
Issue Date: 2013
Publisher: Newcastle University
Abstract: Inherited abnormalities of the kidney are frequently observed and represent a significant cause of morbidity and mortality. The globally increasing number of patients with end- stage renal disease (ESRD) urges the identification of molecular pathways involved in renal pathophysiology, to serve as targets for therapeutic intervention. Data from 2010 estimates the Saudi Arabian population to be 27 million, with one of the highest growth rates in the world. The population is characterized with high consanguinity rate, large family size, and a tribal structure. The consanguinity rate results in a high incidence of autosomal recessive genetic disorders. The population is at high risk of renal failure, with 133 incident cases per million populations per year that require renal replacement therapy. In such a population, characterization of new kidney disease gene loci using homozygosity mapping and positional cloning within consanguineous families is a powerful strategy. This study aimed to adopt this approach in order to search for known and novel molecular causes of inherited kidney diseases in the Saudi population. We studied patients and families with nephrotic syndrome, renal ciliopathies, nephrocalcinosis and renal agenesis. For nephrotic syndrome, we found that the most common genetic cause was a homozygous mutation in the NPHS2 gene. Novel and reported mutations in known nephrosis genes were detected. In a family with Bardet Biedl Syndrome, we utilized zebrafish and renal epithelial cells to determine the functional significance of a novel BBS5 mutation. In another consanguineous family with an autosomal recessive syndrome of distal renal tubular acidosis, small kidneys, and nephrocalcinosis we identified a novel locus on chromosome 2. We also describe the molecular genetic investigation of families with bilateral renal agenesis. In conclusion, in the highly consanguineous Saudi population we have utilized a variety of genetic approaches to identify and characterize novel genetic variants causing inherited renal disease.
Description: PhD Thesis
Appears in Collections:Institute of Genetic Medicine

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