A Conservative Assessment of the Major Genetic C...
ICP may be defined as chronic pancreatitis in the absence of any obvious precipitating factors（e.g.，alcohol abuse）and a family history of the disease（Chen and Férec 2009）.We have recently attempted to make a conservative assessment of the major genetic causes of ICP in a group of 253 young French patients.To this end，we analysed for the first time not only micro-lesions（comprising coding sequence variants and variants at intron/exon boundaries）but also gross genomic rearrangements in the four firmly established chronic pancreatitis genes［namely PRSS1，SPINK1，CTRC and CFTR（cystic fibrosis transmembrane conductance regulator；OMIM#602421）］.We classified the sequence variants/genotypes into three categories（viz.causative，contributory or neutral）taking into consideration the following four parameters：（ⅰ）their allele frequencies in both patient and normal control populations，（ⅱ）their presumed or experimentally confirmed functional effects，（ⅲ）the relative importance of their associated genes in the pathogenesis of chronic pancreatitis，and（ⅳ）genegene interactions wherever applicable.Adoption of this strategy allowed us to assess the pathogenic relevance of specific variants/genotypes to their respective carriers to an unprecedented degree（Masson et al.2013）.The genetic cause of ICP could be unequivocally assigned in 23.7%of individuals in the study group.A strong genetic susceptibility factor was also identified in an additional 24.5%of cases.Taken together，up to 48.2%of the studied ICP patients were found to display evidence of a genetic basis for their disease phenotype（Masson et al.2013）.(https://www.daowen.com)