title: Identification of a novel mutation in the PNLIP gene in two brothers with congenital pancreatic lipase deficiency.
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.
authors.affiliation: Raphael Recanati Genetics Institute, Schneider Children's Medical Center of Israel, Rabin Medical Center, Petah Tikva, Israel.
authors.forename: Doron M
authors.initials: DM
authors.lastname: Behar
authors.forename: Lina
authors.initials: L
authors.lastname: Basel-Vanagaite
authors.forename: Fabian
authors.initials: F
authors.lastname: Glaser
authors.forename: Marielle
authors.initials: M
authors.lastname: Kaplan
authors.forename: Shay
authors.initials: S
authors.lastname: Tzur
authors.forename: Nurit
authors.initials: N
authors.lastname: Magal
authors.forename: Tal
authors.initials: T
authors.lastname: Eidlitz-Markus
authors.forename: Yishay
authors.initials: Y
authors.lastname: Haimi-Cohen
authors.forename: Galit
authors.initials: G
authors.lastname: Sarig
authors.forename: Concetta
authors.initials: C
authors.lastname: Bormans
authors.forename: Mordechai
authors.initials: M
authors.lastname: Shohat
authors.forename: Avraham
authors.initials: A
authors.lastname: Zeharia
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008049:Lipase / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D020125:Mutation, Missense; D010179:Pancreas / Q000201:enzymology*; D011487:Protein Conformation; D035781:Siblings; D055815:Young Adult
chemical_list: D008049:Lipase; C518354:PNLIP protein, human
keywords: Arab; absorption; consanguineous; dietary fat