1. An Updated Mutation Spectrum of the ?-Secretase Complex: Novel NCSTN Gene Mutation in an Indian Family with Hidradenitis Suppurativa and Acne Conglobata.
- Author
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Ratnamala, Uppala, Jain, Nayan K., Jhala, Devendrasinh D., Prasad, Pullabatla V. S., Saiyed, Nazia, Nair, Sreelatha, and Radhakrishna, Uppala
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ACNE ,GENETIC mutation ,PAPER chromatography ,PROTEOLYTIC enzymes ,GENETIC testing ,MEDICAL genetics ,HIDRADENITIS suppurativa ,SPECTRUM analysis ,LONGITUDINAL method - Abstract
Background: Hidradenitis suppurativa (HS) is a complex, chronic inflammatory skin disorder whose pathophysiology is poorly understood. Genetic studies have shown that HS is predisposed by mutations in the γ-secretase gene, but only a proportion of familial and partial sporadic cases have been shown to possess such mutations. HS has high genetic heterogeneity and is thought to be triggered by a combination of genetics and environmental factors. Aims: The study aimed to investigate the genetic causes of HS in a large cohort of patients and to update the mutation spectrum of γ-secretase complex genes. Methods: We conducted mutational screening of 95 sporadic HS cases and one large family with both HS and acne conglobata (AC) to identify mutations in the coding and splice junction region of γ-secretase complex genes (nicastrin (NCSTN), presenilin 1 (PSEN1), presenilin enhancer 2 (PSENEN), and aph-1 homolog B, gamma-secretase subunit (APH1B)). Results: Our study identified a nucleotide substitution of 1876C>T in the NCSTN gene, which caused a stop codon (p. Arg626X) in the affected members of a large family with HS and AC. No pathogenic variants were detected in 95 sporadic cases of HS, indicating there is possible genetic heterogeneity. Conclusion: We report a new family with a nonsense mutation in the NCSTN gene that supports the role of the γ-secretase complex genes in HS with AC. The updated γ-secretase mutation spectrum for HS now includes 78 mutations. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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