Severe infantile isolated exocrine pancreatic insufficiency caused by the complete functional loss of the SPINK1 gene

Venet, Théa, Masson, Emmanuelle, Talbotec, Cécile, Billiemaz, Kareen, Touraine, Renaud, Gay, Claire, Destombe, Sylvie, Cooper, David ORCID: https://orcid.org/0000-0002-8943-8484, Patural, Hugues, Chen, Jian-Min and Férec, Claude 2017. Severe infantile isolated exocrine pancreatic insufficiency caused by the complete functional loss of the SPINK1 gene. Human Mutation 38 (12) , pp. 1660-1665. 10.1002/humu.23343

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Abstract

Exocrine pancreatic insufficiency (EPI) is rare in children, with most if not all cases occurring as part of syndromic conditions such as cystic fibrosis and Shwachman–Diamond syndrome. Here we report two cases, both presenting with severe EPI around 5 months of age. Characterized by diffuse pancreatic lipomatosis, they otherwise exhibited no remarkable deficiencies in other organs. Novel non-identical homozygous variants (a deletion removing the entire SPINK1 gene and an insertion of a full-length inverted Alu element into the 3′-untranslated region of the SPINK1 gene) resulting in the complete functional loss of the SPINK1 gene (encoding pancreatic secretory trypsin inhibitor) were identified in each patient. Having correlated our findings with current knowledge of SPINK1's role in exocrine pancreas pathophysiology, we propose that complete and partial functional losses of the SPINK1 gene are associated with quite distinct phenotypes, the former causing a new pediatric disease entity of severe infantile isolated EPI.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Wiley-Blackwell
ISSN:	1059-7794
Date of First Compliant Deposit:	18 October 2017
Date of Acceptance:	18 September 2017
Last Modified:	03 Dec 2024 10:00
URI:	https://orca.cardiff.ac.uk/id/eprint/105641

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