Identification of a novel mutation in the PNLIP gene in two brothers with congenital pancreatic lipase deficiency

Doron M. Behar, Lina Basel-Vanagaite, Fabian Glaser, Marielle Kaplan, Shay Tzur, Nurit Magal, Tal Eidlitz-Markus, Yishay Haimi-Cohen, Galit Sarig, Concetta Bormans, Mordechai Shohat, Avraham Zeharia

Research output: Contribution to journalArticlepeer-review

Abstract

Congenital pancreatic lipase (PNLIP) deficiency is a rare monoenzymatic form of exocrine pancreatic failure characterized by decreased absorption of dietary fat and greasy voluminous stools, but apparent normal development and an overall good state of health. While considered to be an autosomal recessive state affecting a few dozens of individuals world-wide and involving the PNLIP gene, no causative mutations for this phenotype were so far reported. Here, we report the identification of the homozygote missense mutation, Thr221Met [c.662C>T], in two brothers from a consanguineous family of Arab ancestry. The observed genotypes among the family members were concordant with an autosomal recessive mode of inheritance but moreover a clear segregation between the genotype state and the serum PNLIP activity was evident. Based on biophysical computational tools, we suggest the mutation disrupts the protein's stability and impairs its normal function. Although the role of PNLIP is well established, our observations provide genetic evidence that PNLIP mutations are causative for this phenotype. -Behar, D. M., L. Basel-Vanagaite, F. Glaser, M. Kaplan, S. Tzur, N. Magal, T. Eidlitz-Markus, Y. Haimi-Cohen, G. Sarig, C. Bormans, M. Shohat, and A. Zeharia. Identification of a novel mutation in the PNLIP gene in two brothers with congenital pancreatic lipase deficiency.

Original languageEnglish
Pages (from-to)307-312
Number of pages6
JournalJournal of Lipid Research
Volume55
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • Absorption
  • Arab
  • Consanguineous
  • Dietary fat

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