Isolated choanal and gut atresias: pathogenetic role of serine protease inhibitor type 2 (SPINT2) gene mutations unlikely

Eur J Med Res. 2018 Mar 2;23(1):13. doi: 10.1186/s40001-018-0312-2.


Background: Choanal (CA) and gastrointestinal atresias (GA) are an important feature of syndromic congenital sodium diarrhea (sCSD), a disorder recently associated with mutations in the gene for serine protease inhibitor type 2 (SPINT2). It is, however, not known whether isolated non-syndromic CA and GA themselves might result from SPINT2 mutations.

Methods: We performed a prospective cohort study to investigate 19 CA and/or GA patients without diarrhea ("non-sCSD") for potential sCSD characteristic clinical features and SPINT2 mutations.

Results: We found a heterozygous SPINT2 splice mutation (c.593-1G>A), previously demonstrated in sCSD in homozygous form, in only 1 of the 19 patients of the "non-sCSD" cohort. This patient presented with isolated anal atresia and borderline low laboratory parameters of sodium balance. In the remaining 18 non-sCSD CA/GA patients investigated, SPINT2 sequence analysis and clinical markers of sodium homeostasis were normal. None of the 188 healthy controls tested in a regional Tyrolean population harbored the c.593-1G>A mutation, which is also not listed in the ExAc and gnomAD databases.

Conclusions: The finding of only one heterozygous SPINT2 mutation in 19 patients with isolated CA/GA was not statistically significant. Therefore, SPINT2 mutations are an unlikely cause of non-sCSD atresia. Trial registration ISRCTN73824458. Retrospectively registered 28 September 2014.

Keywords: Choanae; Gut; Isolated atresia; SPINT2 splice mutation; Serine protease inhibitor type 2.

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Adult
  • Diarrhea / congenital*
  • Diarrhea / genetics
  • Female
  • Humans
  • Male
  • Membrane Glycoproteins / drug effects
  • Membrane Glycoproteins / genetics*
  • Metabolism, Inborn Errors / genetics*
  • Mutation / genetics*
  • Prospective Studies
  • Serine Proteinase Inhibitors / therapeutic use


  • Membrane Glycoproteins
  • SPINT2 protein, human
  • Serine Proteinase Inhibitors

Supplementary concepts

  • Diarrhea 3, Secretory Sodium, Congenital

Associated data

  • ISRCTN/ISRCTN73824458