Identification of a comprehensive spectrum of genetic factors for XXXX in a chinese population by next-generation sequencing.

@entity1 @entity0 @entity5 @entity5345 @entity2674 @entity5962 @entity876 @entity6069 @entity23151 @entity4310 @entity11807
The genetic etiology of @entity0 has not been fully elucidated. Although germline mutations of high-penetrance genes such as @entity6069 are implicated in development of @entity0 , at least half of all @entity0 families are not linked to these genes. To identify a comprehensive spectrum of genetic factors for @entity0 in a Chinese population, we performed an analysis of germline mutations in 2,165 coding exons of 152 genes associated with @entity4310 using next-generation sequencing (NGS) in 99 @entity0 @entity1 from families of @entity5 @entity1 regardless of @entity5 types. Forty-two deleterious germline mutations were identified in 21 genes of 34 @entity1 , including 18 (18.2%) @entity5345 or @entity2674 mutations, 3 (3%) @entity876 mutations, 5 (5.1%) DNA mismatch repair gene mutations, 1 (1%) @entity5962 mutation, 6 (6.1%) @entity11807 pathway gene mutations, and 9 (9.1%) mutations in other genes. Of seven @entity1 who carried mutations in more than one gene, 4 were @entity5345 /2 mutation carriers, and their average onset age was much younger than @entity1 with only @entity6069 mutations. Almost all identified high-penetrance gene mutations in those families fulfill the typical phenotypes of @entity4310 listed in the National @entity5 Network (NCCN) guidelines, except two @entity876 and three mismatch repair gene mutations. Furthermore, functional studies of @entity23151 germline mutations confirmed the association between @entity23151 mutation and tumorigenesis, and segregation analysis suggested antagonism between @entity5345 and @entity23151 . We also identified a lot of low-penetrance gene mutations. Although the clinical significance of those newly identified low-penetrance gene mutations has not been fully appreciated yet, these new findings do provide valuable epidemiological information for the future studies. Together, these findings highlight the importance of genetic testing based on NCCN guidelines and a multi-gene analysis using NGS may be a supplement to traditional genetic counseling.
