A De Novo <i>CaSR</i> Missense Variant in Combination with Two Inherited Missense Variants in <i>CFTR</i> and <i>SPINK1</i> Detected in a Patient with Chronic Pancreatitis
Piera Bontempo,
Cecilia Surace,
Lucia Menale,
Claudia Alicata,
Gemma D’Elia,
Anna Cristina Tomaiuolo,
Daniele Minervino,
Elisa Lorefice,
Antonio Novelli
Affiliations
Piera Bontempo
Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), 00146 Rome, Italy
Cecilia Surace
Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), 00146 Rome, Italy
Lucia Menale
Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), 00146 Rome, Italy
Claudia Alicata
Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), 00146 Rome, Italy
Gemma D’Elia
Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), 00146 Rome, Italy
Anna Cristina Tomaiuolo
Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), 00146 Rome, Italy
Daniele Minervino
Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), 00146 Rome, Italy
Elisa Lorefice
Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), 00146 Rome, Italy
Antonio Novelli
Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), 00146 Rome, Italy
Chronic pancreatitis is often secondary to alcohol abuse, but pancreatitis with no other aetiology is frequently associated with variants in genes encoding proteins related to zymogen granule activation. Our goal was to identify genomic variants in a patient by analyzing an extended panel of genes associated with the intra-pancreatic activation of the trypsin pathway. A 23-year-old woman was addressed at our institution because of chronic pancreatitis of unknown aetiology presenting recurrent episodes since she was the age of four. Next Generation Sequencing was performed to analyze a panel of nine genes associated with pancreatitis (CaSR, CFTR, CPA1, CTRC, CTSB, KRT8, PRSS1, PRSS2, and SPINK1). Three missense variants were found: p.Leu997Phe, maternally inherited, in the CFTR gene; p.Ile73Phe, paternally inherited, in the SPINK1 gene; and p.Phe790Ser, a de novo variant, in the CaSR gene. They were classified, respectively as probably benign, a Variant of Uncertain Significance, and the last one, which has never been described in the literature, as likely being pathogenic following American College of Medical Genetics and Genomics standard guidelines. Extensive intra-pancreatic activation of trypsin pathway gene sequencing detected rare variants that were not found with other gene screening and showed that variants in different genes may interact in contributing to the onset of the pancreatitis phenotype.