Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Bierbaumer, S.
Molecular characterization of two consanguineous Pakistani families with Bardet-Biedl syndrome.
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2020. pp. 70
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Lafer Ingrid
- Windpassinger Christian
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- Abstract:
- Introduction: Bardet-Biedl syndrome is an autosomal-recessive disorder characterized by retinal dystrophy, polydactyly, central obesity, mental retardation, hypogonadism and renal dysfunction. It belongs to the group of ciliopathies, as defects in the primary cilium lead to disease manifestation. To date, 24 genes are known to cause the disorder. Methods: Two consanguineous Pakistani families were molecularly characterized to identify the disease causing variant. The most frequently mutated genes in Bardet-Biedl Syndrome (BBS1 and BBS10) were investigated for homozygosity using microsatellite markers. Both affected individuals were then sequenced by whole exome sequencing, and segregation of the candidate variant within the families was confirmed by Sanger sequencing. Results: Whole exome sequencing identified a recently reported homozygous deletion in BBS9 in both individuals. This deletion leads to a shift in the reading frame and to the premature termination of the protein synthesis. As the segment harboring the variant was identical in both individuals, ancestry of the families was explored for more ancient relation and a possible relation with the Khaisoori tribe was established for both. Discussion: Bardet-Biedl syndrome is a genotypically and phenotypically divers disorder. Both individuals of this study exhibit a variable severity of the phenotype, despite harboring the same genotype. This is most dramatically seen in the different severity of intellectual disability. This report extends the clinical and genetic description of Bardet-Biedl syndrome and describes the possibility of a founder mutation in the Khaisoori tribe, which should be taken into account for the molecular diagnosis of affected individuals.