European Journal of Medical Research (2018-03-01)

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

  • Christian Niederwanger,
  • Silvia Lechner,
  • Lisa König,
  • Andreas R. Janecke,
  • Claus Pototschnig,
  • Beatrice Häussler,
  • Sabine Scholl-Bürgi,
  • Thomas Müller,
  • Peter Heinz-Erian

Journal volume & issue
Vol. 23, no. 1
pp. 1 – 7


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Abstract 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