SERPING1 exon 3 splicing variants using alternative acceptor splice sites

SERPING1 mutation update: Mutation spectrum and C1 Inhibitor phenotypes

“…Variants affecting splice sites and those in splicing regulatory elements, incl enhancers, and silencers, can impair premessenger RNA (pre‐mRNA) splicing, eventually leading to a severe phenotype, as suggested by Grodecká et al (). SERPING1 is a naturally alternatively spliced gene, with in particular a highly variable abundance and a subtle regulation of exon 3 skipping (De la Cruz, López‐Lera, & López‐Trascasa, ; Grymová, Grodecká, Souček, & Freiberger, ). Despite the availability of many prediction tools, prognosis of splicing affection is not trivial, especially when regulatory elements are involved.…”

Complex analysis of the national Hereditary angioedema cohort in Slovakia – Identification of 12 novel variants in SERPING1 gene

“…Exon 3 skipping in hepatic cells and monocytes of healthy humans was already reported in the literature with presence in approximately one-third of all transcripts. 45 , 54 The proportion of full-length and exon 3 skipped splicing isoforms has probably impact on the overall C1–INH level. 54 We suppose that this variant identified in our cohort causes the dysregulation of the splicing isoforms balance which leads to the decrease of full-length protein level and the development of severe course of the disease.…”

Hereditary angioedema caused by a novel intronic variant of SERPING1

“…We propose that this absence in monocytes is due to the effect of the mutation added to the alternative splicing. Despite that, we cannot exclude its presence in other tissues as the liver, which is the main producer of C1 INH protein, and the existence of alternative splicing in these cells is not clear 5,6 . However, we cannot study these transcripts in liver cells because it is an invasive procedure for children.…”

“…It has been reported the constitutive alternative splicing of mRNA SERPING1 gene in some studies 5‐7 consisting in the absence of exon 3 but its relevance remains unknown. De la Cruz et al found differences in the quantity of this alternative transcript in monocytes between HAE patients depending on the type of mutation, presenting a decrease in the full‐length variant in those patients with mutations altering splicing 7 …”