Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Tatrai, B.
Genetic analysis of two consanguineous Pakistani families with rare hereditary skin diseases
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2022. pp. 64
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Lafer Ingrid
- Windpassinger Christian
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- Abstract:
- Introduction: Hereditary skin diseases can be caused by mutations in a multitude of genes, with both dominant and recessive forms of inheritance. Depending on the mutation, the resulting skin changes can vary wildly and be syndromic or non-syndromic. For this diploma-thesis, two different, consanguineous Pakistani families with hereditary skin diseases were recruited for genetic testing. In family 1, affected individuals presented with alopecia/woolly hair, dry skin, and nail changes. In family 2, the main symptom was dry skin with formation of abscess-like lesions upon exposure to sunlight. Materials and Methods: DNA samples were extracted from affected and healthy individuals in both families. Whole Exome Sequencing was performed, and this data was used to identify homozygous regions. The data acquired through these procedures was used to identify potentially pathogenic variants in candidate genes. Segregation of these variants was verified using Sanger sequencing. Results: For family 1, the known mutation c.1493C>T (p.Pro498Leu) in the DSP gene was identified as a causative mutation for alopecia. For family 2, a novel candidate variant was found in the CARMIL2 gene: c.677A>T (p.Asp226Val). In addition, a known version of G6PD deficiency was identified in this family. Discussion: The mutation c.1493C>T of the DSP gene was first described by Jan et al. in 2015. The phenotype described in their paper is for the most part identical to the phenotype of family 1 of this thesis. The clinical spectrum of this mutation could be expanded through the correlation of the cases described here, but further research, including cell biological studies, is still required to better comprehend the pathomechanisms of this mutation. The variant c.677A>T of the CARMIL2 gene has not been described in literature. No causal connection with the observed phenotype can be established with our findings. Further research is necessary to evaluate the potential pathogenicity of this variant.