Identification of seven novel mutations including the first two genomic rearrangements in SLC26A3 mutated in congenital chloride diarrhea

Congenital chloride diarrhea (CLD) is an autosomal recessive disorder chara cterized by defective intestinal electrolyte absorption, resulting in volum inous osmotic diarrhea with high chloride cone tent. A variety of mutations in the solute carrier family 26, member 3 gene (SLC26A3, previously known as CLD or DRA) are responsible for the disease. Since the identification of the SLC26A3 gene and the determination of its genomic structure, altogethe r three founder and 17 private mutations have been characterized within mis cellaneous ethnic groups. We screened for mutations in seven unrelated fami lies with CLD. The diagnoses were confirmed by fecal chloride measurements. The combined PCR-SSCP and sequencing analyses revealed altogether seven no vel mutations including two missense mutations (S206P, D468V), two splicing defects (1VS12-1G>C, IVS13-2delA), one nonsense mutation (Q436X), one inse rtion/deletion mutation (2104-2105delGGins29-bp), and an intragenic deletio n of SLC26A3 exons 7 and 8. Two previously identified mutations were also f ound. This is the first report of rearrangement mutations in SLC26A3. Molec ular features predisposing SLC26A3 for the two rearrangements may include r epetitive elements and palindromic-like sequences. The increasingly wide di versity of SLC26A3 mutations suggests that mutations in the SLC26A3 gene ma y not be rare events. Hum Mutat 18:233-242, 2001. (C) 2001 Wiley-Liss, Inc.