Congenital chloride diarrhea (CLD) is an inherited intestinal disorder caused by mutations in the down-regulated in adenoma gene. In Finland, the disease is prevalent because of a founder effect, and all but one of the CLD-associated chromosomes carry the same mutation, V317del. In Poland, another area with a high incidence of CLD, as many as seven different mutations have been detected so far. A third known cluster of CLD, around the Persian Gulf, has not been genetically studied. We studied the allelic diversity of CLD in Poland, in Saudi Arabia and Kuwait, and in three isolated families from North America and Hong Kong. Altogether, eight novel mutations were identified, making a total of 19 known CLD gene mutations. The Polish major mutation I675-676ins was found in 47% of the Polish CLD-associated chromosomes. Haplotype analysis and clustering of the I675-676ins mutation supported a founder effect and common ancestral origin. As in Finland, a major founder effect was observed in Arab patients: 94% of the CLD-associated chromosomes carried a nonsense mutation, G187X, which occurred in either a conserved ancestral haplotype or its derivative. Our data confirm that the same locus is mutated in all cases of CLD studied so far. In Poland, a relatively common founder mutation is likely to highlight a set of rare mutations that would very rarely produce homozygosity alone. This suggests that mutations in the CLD locus are not rare events. Although the disease is thought to be rare, undiagnosed patients may not be uncommon.
Published epidemiologic data on the administration rates of enteral/parenteral home nutrition is very limited. The aim of this first nationwide study was to assess the availability of pediatric home enteral nutrition (HEN) services in Poland. The questionnaire was sent to all regional centers providing pediatric HEN services in Poland (n = 14). The analysis included the number of pediatric patients who received HEN in 2010, their demographic characteristics and geographical distribution. Furthermore, the distributions of indications and methods of enteral nutrition administration were analyzed, along with the reasons of withdrawal from the HEN program. The number and fraction of children receiving HEN increased in 2010, from 433 (11.34 per 1 million inhabitants) on January 1st to 525 (13.75) on December 31st. Marked differences were observed in geographical distribution of this parameter, from zero to up to 30 pediatric patients per 1 million inhabitants. Median age of patients was 6 years (range: 9 months–18 years). In most cases, HEN was prescribed due to neurological disorders (n = 337, 64.2%), and administered by means of gastrostomy (n = 450, 85.71%). This study revealed the dynamic development of pediatric HEN services in Poland but also documented their potential regional shortages.
An inherited defect in intestinal anion exchange, congenital chloride diarrhea (CLD), was recently shown to be caused by mutations in the down-regulated in adenoma (DRA) gene. A three base pair deletion resulting in the loss of an amino acid valine (V317del) in the predicted CLD/DRA protein was shown to be responsible for all CLD cases in a Finnish founder population. Two additional mutations, H124L and 344delT, were found in Polish CLD patients. Here, we screened for additional mutations in a set of 14 CLD families of Polish, Swedish, North American, and Finnish origin using primers that allowed mutation searches directly from genomic DNA samples. We found eight novel mutations in the CLD/DRA gene. The mutations included two transversions, one transition, one insertion, and four small deletions. Of 11 sequence alterations detected so far, nine lie clustered in three short segments that are 49 bp, 39 bp, and 65 bp in size, respectively. These short segments span only 6.7% of the total cDNA length, suggesting functional importance or mutation-prone DNA regions of the corresponding CLD/DRA protein domains.
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