Biallelic mutations in FLG, TGM1, and STS genes segregated with different types of ichthyoses in eight families of Pakistani origin

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.

Do crop diversity and livestock production improve smallholder intra-household dietary diversity, nutrition and sustainable food production? Empirical evidence from Pakistan

“…Due to limited resources, low income, and subsistence farming, the farm diversification of households has declined (Saqib et al, 2018;Fahad and Wang, 2020). Simultaneously, family members of farming households are quitting the business, expanding the breadth of economic opportunities for rural families in Pakistan (Usman et al, 2016;Drucza and Peveri, 2018;Khan et al, 2020). Currently, 70% of Pakistan's average farm family's income comes from the agriculture sector (Peerzado et al, 2019;Jamil et al, 2021b).…”