Biallelic mutations in FLG, TGM1, and STS genes segregated with different types of ichthyoses in eight families of Pakistani origin. (15th February 2023)

• Record Type: Journal Article
• Authors: Khan, Niamatullah; Shah, Khadim; Fozia, Fozia; Khan, Sher A.; Muhammad, Nazif; Nasir, Abdul; Ahmad, Ijaz; Rehman, Zia U.; Jan, Abid; Muhammad, Noor; Khan, Saadullah
• Is Part Of: International journal of dermatology. Volume 62:Number 5(2023)
• Page Start: 672
• Page End: 680
• Publication Date: 2023-02-15
• Subjects: Dermatology -- Periodicals; 616.5
• DOI: 10.1111/ijd.16614
• Languages: English
• ISSNs: 0011-9059

Abstract

Abstract: Background: Congenital ichthyosis is a diverse group of keratinization disorders associated with generalized scaling of skin of varying severity. The non‐syndromic forms of congenital ichthyosis are further grouped into common ichthyosis (ichthyosis vulgaris and X‐linked ichthyosis), autosomal recessive congenital ichthyosis, and keratopathic ichthyosis. Objective: To identify sequence variants involved in different forms of hereditary ichthyoses. Methods: We studied eight families with different types of ichthyosis including four families with autosomal recessive congenital ichthyosis and four families with common ichthyosis. Whole exome sequencing and PCR based genotyping was carried out to find out the molecular basis of disease. Results: In one family, a novel duplication sequence variant NM_002016.2:c.2767dupT; NP_002007.1:p.Ser923PhefsTer2 was identified in FLG gene; in four families a previously reported nonsense sequence variant NM_000359.3:c.232C>T; NP_002007.1:p.Arg78Ter was identified in TGM1 gene, while, in three families of X‐linked recessive ichthyosis, the whole STS gene (NM_001320752.2; NP_001307681.2) regions were deleted. Study limitation: Gene expression studies have not been performed that would have strengthened the findings of computational analysis. Conclusion: This study highlights the significance of the c.232C>T variant in the TGM1 gene as a possible founder mutation, complete STS gene deletion as reported previously in Pakistani population, while novel sequence variant in the FLG gene expands the spectrum of variations in this gene. These findings may be used for genetic counseling of the studied families.