Twelve Novel Mutations in the SLC26A3 Gene in 17 Sporadic Cases of Congenital Chloride Diarrhea. Issue 1 (July 2017)

• Record Type: Journal Article
• Authors: 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; Berni Canani, Roberto
• Is Part Of: Journal of pediatric gastroenterology and nutrition. Volume 65:Issue 1(2017)
• Publication Date: 2017-07
• Subjects: chloride losing diarrhea -- diarrhea anion exchanger -- genotype -- mutations -- member 3 of solute carrier family 26 -- splicing effect; Children -- Nutrition -- Periodicals; Pediatric gastroenterology -- Periodicals; Infants -- Nutrition -- Periodicals; Nutrition disorders in children -- Periodicals; Child Nutrition -- Periodicals; Digestive System -- growth & development -- Periodicals; Gastrointestinal Diseases -- Periodicals; Infant Nutrition -- Periodicals; Nutrition Disorders -- Periodicals; Child; 618.923
• DOI: 10.1097/MPG.0000000000001418
• Languages: English
• ISSNs: 0277-2116

Abstract

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 CCD 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.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 6 novel missense mutations. Conclusions: We confirm the molecular heterogeneity of sporadic CCD 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. Abstract : Supplemental Digital Content is available in the text