1. Twelve Novel Mutations in the SLC26A3 Gene in 17 Sporadic Cases of Congenital Chloride Diarrhea
- Author
-
Sabrina Cardile, Vincenza Pezzella, Licia Lugli, Giuseppe Castaldo, Ausilia Elce, Roberto Berni Canani, Sonia Giordano, Manuela Scorza, Marika Comegna, Claudio Romano, Renato Liguori, Giuseppe Cardillo, Laura Lucaccioni, Felice Amato, Amato, Felice, Cardillo, Giuseppe, Liguori, Renato, Scorza, Manuela, Comegna, Marika, Elce, Ausilia, Giordano, Sonia, Lucaccioni, Laura, Lugli, Licia, Cardile, Sabrina, Romano, Claudio, Pezzella, Vincenza, Castaldo, Giuseppe, and BERNI CANANI, Roberto
- Subjects
Diarrhea ,Genetic Markers ,0301 basic medicine ,Genotype ,Genotyping Techniques ,Congenital chloride diarrhea ,In silico ,SLC26A3 ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Missense mutation ,Chloride-Bicarbonate Antiporters ,Genetic Testing ,Gene ,Genetics ,biology ,Gastroenterology ,medicine.disease ,030104 developmental biology ,Sulfate Transporters ,Case-Control Studies ,Mutation ,chloride losing diarrhea ,diarrhea anion exchanger ,genotype ,member 3 of solute carrier family 26 ,mutations ,splicing effect ,Metabolism, Inborn Errors ,Pediatrics, Perinatology and Child Health ,RNA splicing ,biology.protein ,Gastroenterology, chloride losing diarrhea, diarrhea anion exchanger, mutations, SLC26A3, splicing effect ,030211 gastroenterology & hepatology ,Minigene - Abstract
Objectives: We aimed to improve the knowledge of pathogenic mutations in sporadic cases of congenital chloride diarrhea (CCD) and emphasize the importance of functional studies to define the effect of novel mutations. Methods: All member 3 of solute carrier family 26 (SLC26A3) coding regions were sequenced in 17 sporadic patients with CCD. Moreover, the minigene system was used to analyze the effect of 2 novel splicing mutations. Results: We defined the SLC26A3 genotype of all 17 patients with CDD and identified 12 novel mutations. Using the minigene system, we confirmed the in silico prediction of a complete disruption of splicing pattern caused by 2 of these novel mutations: the c.971þ3_971þ4delAA and c.735þ4_c.735þ7delAGTA. Moreover, several prediction tools and a structure-function prediction defined the pathogenic role of 6 novel missense mutations. Conclusions: We confirm the molecular heterogeneity of sporadic CDD adding 12 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
- Published
- 2017
- Full Text
- View/download PDF