Mutational analysis of the DTDST gene in a fetus with achondrogenesis type 1B

Cai, Guiming; Nakayama, Masahiro; Hiraki, Yuji; Ozono, Keiichi

doi:10.1002/(sici)1096-8628(19980616)78:1<58::aid-ajmg12>3.3.co;2-f

Cited by 6 publications

(10 citation statements)

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“…(5,(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). Mouse studies have revealed additional roles for these Slc26 proteins in mammalian physiology: deafness, goiter, and acidosis (Slc26a4, pendrin) (42-44), cochlear motor protein (Slc26a5, prestin) (45)(46)(47), proximal tubule NaCl absorption, nephrolithiasis, and intestinal HCO 3 Ϫ secretion (Slc26a6, Pat-1, CFEX) (8, 48 -52), sperm motility (Slc26a8, Tat-1) (53), and gastric acid secretion (Slc26a9) (14).…”

Section: Discussionmentioning

confidence: 99%

Slc26a9 Is Inhibited by the R-region of the Cystic Fibrosis Transmembrane Conductance Regulator via the STAS Domain

Chang

Plata

Sinđić

et al. 2009

Journal of Biological Chemistry

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SLC26 proteins function as anion exchangers, channels, and sensors. Previous cellular studies have shown that Slc26a3 and Slc26a6 interact with the R-region of the cystic fibrosis transmembrane conductance regulator (CFTR), (R)CFTR, via theSlc26 genes and proteins have attracted the attention of physiologists and geneticists. Why? Slc26a1 (Sat-1) was characterized as a Na ϩ -independent SO 4 2Ϫ transporter (1). Given the transport characteristics of the founding member of the gene family, Slc26 proteins were assumed to be sulfate transporters. Disease phenotypes, clone characterization, and family additions demonstrate that the Slc26 proteins are anion transporters or channels (2-4). These proteins have varied tissue expression patterns. At one extreme, Slc26a5 in mammals is found in the hair cells of the inner ear (5), whereas Slc26a2 (DTDST) is virtually ubiquitous in epithelial tissues (2).Several Slc26 proteins are found in the epithelia of the lung, intestine, stomach, pancreas, and kidney, usually in apical membranes. Interestingly these are also tissues and membranes in which the cystic fibrosis transmembrane conductance regulator (CFTR) 5 has been found functionally or by immunohistochemistry. Ko and co-workers (6 -8) examined the distribution of Slc26a3 and Slc26a6 in HCO 3 Ϫ secretory epithelia, and asked if an interaction might occur between these Slc26 proteins and CFTR. In particular, these studies indicate that in expression systems, there is a reciprocal-stimulatory interaction of the STAS (sulfate transporter anti-sigma) domains of Slc26a3 and Slc26a6 with the regulatory region (R-region) of CFTR. These investigators hypothesized that this stimulatory interaction could account for the differences in pancreatic insufficiency and sufficiency observed in cystic fibrosis patients. Nevertheless, knock-out Slc26a6 mouse studies reveal more complicated cell and tissue physiology (see "Discussion").Slc26a9 has been reported to be a Cl Ϫ -HCO 3 Ϫ exchanger (9, 10) or a large Cl Ϫ conductance (3,11,12). Loriol and co-workers (12) indicated that SLC26A9 has a Cl Ϫ conductance that may be stimulated by HCO 3 Ϫ . Two other groups have indicated that the Cl Ϫ conductance is not affected by the presence of HCO 3 Ϫ (10, 11). We have recently demonstrated that Slc26a9 functions as both an electrogenic nCl Ϫ -HCO 3 Ϫ exchanger and a Cl Ϫ channel (10). Dorwart and colleagues (11) found that WNK kinases inhibited the SLC26A9 Cl Ϫ conductance but that this effect was independent of kinase activity. One group has a preliminary report indicating that WNK3 decreased Cl Ϫ uptake,

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Section: Discussionmentioning

confidence: 99%

Slc26a9 Is Inhibited by the R-region of the Cystic Fibrosis Transmembrane Conductance Regulator via the STAS Domain

Chang

Plata

Sinđić

et al. 2009

Journal of Biological Chemistry

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“…Table 1 lists DTDST mutations identified so far in patients and families with DTDST chondrodysplasias, including those reported pre-viously [Hastbacka et al, 1994;Hastbacka et al, 1999;Rossi et al, 1998;Superti-Furga et al, 1996a]; Figure 2 shows their position along the DTDST protein. Direct proof of pathogenicity has not been obtained, except for IVS1+2T>C and 418delT, which have been shown to cause reduced mRNA levels [Hastbacka et al, 1999;Rossi et al, 1996b], and 1045-1047delGTT, which has been shown to abolish DTDST activity in a Xenopus oocyte model [Cai et al, 1998]. However, assumption of pathogenicity is justified in that some predict a truncated polypeptide chain, and others affect amino acids which are either in transmembrane domains or are conserved in man, mouse, and rat (with the exception of 256A>C [N77H], where both mouse and rat have serine).…”

Section: Mutation Analysis Of Dtdst: Methodsmentioning

confidence: 99%

Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene (SLC26A2): 22 novel mutations, mutation review, associated skeletal phenotypes, and diagnostic relevance

Rossi¹,

Superi-Furga²

2001

Hum. Mutat.

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“…Both these mutations have been previously identified in DTDST-related disorders R279W in DTD and AOII and V340del in ACG1B. [3][4][5][6][7]13 In the one family carrying no copies of DTDST Fin , the patient was a compound heterozygote for R279W/V340del.…”

Section: Mutation Analysis Of Patientsmentioning

confidence: 99%

Identification of the Finnish founder mutation for diastrophic dysplasia (DTD)

et al. 1999

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Diastrophic dysplasia (DTD) is especially prevalent in Finland and the existence of a founder mutation has been previously inferred from the fact that 95% of Finnish DTD chromosomes have a rare ancestral haplotype found in only 4% of Finnish control chromosomes. Here we report the identification of the Finnish founder mutation as a GT-> GC transition (c.-26 + 2T > C) in the splice donor site of a previously undescribed 5'-untranslated exon of the diastrophic dysplasia sulfate transporter gene (DTDST); the mutation acts by severely reducing mRNA levels. Among 84 DTD families in Finland, patients carried two copies of the mutation in 69 families, one copy in 14 families, and no copies in one family. Roughly 90% of Finnish DTD chromosomes thus carry the splice-site mutation, which we have designated DTDST Fin . Unexpectedly, we found that nine of the DTD chromosomes having the apparently ancestral haplotype did not carry DTDST Fin , but rather two other mutations. Eight such chromosomes had an R279W mutation and one had a V340del deletion. We consider the possible implications of presence of multiple DTD mutations on this rare haplotype.

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Mutational analysis of the DTDST gene in a fetus with achondrogenesis type 1B

Cited by 6 publications

References 0 publications

Slc26a9 Is Inhibited by the R-region of the Cystic Fibrosis Transmembrane Conductance Regulator via the STAS Domain

Slc26a9 Is Inhibited by the R-region of the Cystic Fibrosis Transmembrane Conductance Regulator via the STAS Domain

Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene (SLC26A2): 22 novel mutations, mutation review, associated skeletal phenotypes, and diagnostic relevance

Identification of the Finnish founder mutation for diastrophic dysplasia (DTD)

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