Twelve Novel Mutations in the SLC26A3 Gene in 17 Sporadic Cases of Congenital Chloride Diarrhea

OBJECTIVES:: we aimed to improve the knowledge of pathogenic mutations in sporadic cases of congenital chloride diarrhea (CCD) and to emphasize the importance of functional studies to define the effect of novel mutations. METHODS:: all SLC26A3 coding regions were sequenced in 17 sporadic CCD patients. Moreover, the minigene system was used to analyse the effect of two novel splicing mutations. RESULTS:: we defined the SLC26A3 genotype of all 17 CDD patients and we identified twelve novel mutations. Using the minigene system we confirmed the in silico prediction of a complete disruption of splicing pattern caused by two of these novel mutations: the c.971+3_971+4delAA and c.735+4_c.735+7delAGTA. Moreover, several prediction tools and a structure-function prediction defined the pathogenic role of six novel missense mutations. CONCLUSION:: we confirm the molecular heterogeneity of sporadic CDD adding twelve novel mutations to the list of known pathogenic mutations. Moreover, we underline the importance, for laboratories that offer molecular diagnosis and genetic counseling, to perform fast functional analysis of novel mutations.