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Aliso Viejo, CA, United States

Beer S.,Boston University | Zhou J.,Boston University | Szabo A.,Boston University | Keiles S.,Ambry Genetics Corporation | And 3 more authors.
Gut | Year: 2013

Objective: The digestive enzyme chymotrypsin C (CTRC) protects against pancreatitis by promoting degradation of trypsinogen, thereby curtailing potentially harmful trypsinogen activation. Loss-of-function variants in CTRC increase the risk for chronic pancreatitis. The aim of the present study was to perform comprehensive functional analysis of all missense CTRC variants identified to date. Design: We investigated secretion, activity and degradation of 27 published and five novel CTRC mutants. We also assessed the effect of five mutants on endoplasmic reticulum (ER) stress. Results: None of the mutants exhibited a gain of function, such as increased secretion or activity. By contrast, 11 mutants showed marked loss of function, three mutants had moderate functional defects, whereas 18 mutants were functionally similar to wild-type CTRC. The functional deficiencies observed were diminished secretion, impaired catalytic activity and degradation by trypsin. Mutants with a secretion defect caused ER stress that was proportional to the loss in secretion. ER stress was not associated with loss-of-function phenotypes related to catalytic defect or proteolytic instability. Conclusions: Pathogenic CTRC variants cause loss of function by three distinct but mutually non-exclusive mechanisms that affect secretion, activity and proteolytic stability. ER stress may be induced by a subset of CTRC mutants, but does not represent a common pathological mechanism of CTRC variants. This phenotypic dataset should aid in the classification of the clinical relevance of CTRC variants identified in patients with chronic pancreatitis. Source


Trademark
Ambry Genetics Corporation | Date: 2012-03-05

Testing kits containing reagents used to analyze and detect genetic defects which may be implicated in disease for clinical or medical laboratory use; Diagnostic preparations for scientific or research use; Diagnostic preparations for clinical or medical laboratory use; Diagnostic reagents for clinical or medical laboratory use. Medical research; DNA analysis services for research; Scientific research services. Medical screening; Medical testing services for diagnostic or treatment purposes; DNA screening for medical purposes.


Trademark
Ambry Genetics Corporation | Date: 2012-03-05

Testing kits containing reagents used to analyze and detect genetic defects which may be implicated in disease for clinical or medical laboratory use; Diagnostic preparations for scientific or research use; Diagnostic preparations for clinical or medical laboratory use; Diagnostic reagents for clinical or medical laboratory use. Medical research; DNA analysis services for research; Scientific research services. Medical screening; Medical testing services for diagnostic or treatment purposes; DNA screening for medical purposes.


Trademark
Ambry Genetics Corporation | Date: 2013-06-18

Diagnostic preparations for scientific or research use; Diagnostic preparations for clinical or medical laboratory use; Testing kits containing reagents used to analyze and detect genetic defects which may be implicated in disease for clinical or medical laboratory use; Diagnostic preparations for scientific or research use; Diagnostic preparations for clinical or medical laboratory use; Diagnostic reagents for clinical or medical laboratory use. DNA analysis services for scientific and medical research purposes, namely, DNA sequencing services, analyzing DNA sequences for genetic variations across different sample populations, correlating DNA sequence variations of sample populations with data indicating effectiveness of medical treatment of the populations, screening DNA sequences to determine the presence or absence of genetic variations that correlate to effectiveness of a proposed medical treatment, confirming or establishing a genetic disorder, Mendelian disease gene discovery, and DNA analysis services under certification standards; Medical testing for medical research purposes, namely, performing exome sequencing services for researchers performing work in connection with human diseases; Scientific research services, namely, analyzing biological samples including cells and cell extracts for the presence, absence or abundance of nucleic acid, polypeptide or molecular markers associated with cell identity or differentiation, and identifying cell stage by detecting or measuring cell differentiation markers; Medical research; DNA analysis services for research; Scientific research services. Medical testing services for diagnostic or treatment purposes; Medical screening; DNA screening for medical purposes.


Trademark
Ambry Genetics Corporation | Date: 2013-06-11

Testing kits containing reagents used to analyze and detect genetic defects which may be implicated in disease for clinical or medical laboratory use; Diagnostic preparations for scientific or research use; Diagnostic preparations for clinical or medical laboratory use; Diagnostic reagents for clinical or medical laboratory use. Medical research; DNA analysis services for research; Scientific research services. Medical screening; Medical testing services for diagnostic or treatment purposes; DNA screening for medical purposes.

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