Identification of a novel protein truncating mutation p.Asp98* in XPC associated with xeroderma pigmentosum in a consanguineous Pakistani family

Molecular Genetics & Genomic Medicine

Erwin Petek¹  Jasmin Blatterer¹  Christian Windpassinger¹  Erich Schaflinger¹  Safeer Ahmad²  Ejazullah Khan²  Muzammil A. Khan²  Muhammad Z. Ali² 

[1] Diagnostic & Research Institute of Human Genetics Medical University of Graz Graz Austria;Gomal Centre of Biochemistry and Biotechnology Gomal University Dera Ismail Khan Khyber Pakhtunkhwa Pakistan;

关键词: frameshift mutation;    homozygosity mapping;    Pakistani family;    xeroderma pigmentosum;    XPC;   

DOI  :  10.1002/mgg3.1060

来源: DOAJ

【 摘 要 】

Abstract Background Xeroderma pigmentosum (XP) is a rare genetic disorder, which is characterized by hyper‐sensitivity to solar ultraviolet (UV) radiation. Clinical consequences of sun exposure are skin lesions and an increased risk of developing skin cancer. Genetic studies have identified eight genes associated with xeroderma pigmentosum. The proteins encoded by these genes are mainly involved in DNA repair mechanisms. Methods Molecular genetic characterization of patients with xeroderma pigmentosum involved positional cloning methods such as homozygosity mapping and subsequent candidate gene analysis. Mutation screening was performed through Sanger DNA sequencing. Results and Discussion In this case study, we report a novel protein truncating mutation in XPC associated with autosomal recessive xeroderma pigmentosum in a consanguineous Pakistani family. Genetic mapping revealed a novel single base insertion of a thymine nucleotide NM_004628.4: c.291dupT (c.291_292insT) in the second exon of XPC. The identified mutation leads to a premature stop codon (TGA) at amino acid position 98 (p.Asp98*) and thus presumably results in a truncated protein. The Xeroderma pigmentosum, complementation group C (XPC) is located on 3p25.1 and encodes a protein involved in nucleotide excision repair. The identified mutation presumably truncates all functional domains of the XPC protein, which likely results in the loss of protein function. Conclusion The study expands the knowledge of the mutational spectrum of XPC and is valuable for genetic counseling of affected individuals and their families.

【 授权许可】

Unknown