| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Congenital Diarrhoea v1.23 | PNLIP | Zornitza Stark Marked gene: PNLIP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Diarrhoea v1.23 | PNLIP | Zornitza Stark Gene: pnlip has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Diarrhoea v1.23 | PNLIP | Zornitza Stark Classified gene: PNLIP as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Diarrhoea v1.23 | PNLIP | Zornitza Stark Gene: pnlip has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Diarrhoea v1.22 | PNLIP |
Zornitza Stark gene: PNLIP was added gene: PNLIP was added to Congenital Diarrhoea. Sources: Expert Review Mode of inheritance for gene: PNLIP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PNLIP were set to 31977950; 25862608; 24262094; 27604308; 40840699 Phenotypes for gene: PNLIP were set to Pancreatic lipase deficiency MIM#614338 Review for gene: PNLIP was set to AMBER Added comment: PMID 40840699: Six children from four Amish families with novel homozygous PNLIP variant, c.869G>A (p.S290N) and CPLD symptoms. Computational modeling showed that p.Ser290 is highly conserved across species and the variant causes steric hindrance resulting in protein misfolding. Functional assays revealed that the PNLIP variant had a complete loss of activity compared to the wild type (WT), with defects in catalytic function and secretion. Immunoblotting showed reduced PNLIP variant in the medium and increased accumulation in the detergent-insoluble fraction consistent with protein misfolding. Variant-expressing cells had elevated levels of BiP, an ER stress marker, and increased Xbp1 mRNA splicing, suggesting an elevated ER stress and unfolded protein response (UPR). Previous reports: 4 cases from 2 unrelated families, with supporting biochemical assays in patient cells and cellular-based assays. The cases have decreased absorption of dietary fat and greasy voluminous stools, but apparent normal development and an overall good state of health. AMBER rating as not quite as severe as the other conditions included in this panel. Sources: Expert Review |
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