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.

Congenital chloride diarrhea (CLD) is an autosomal recessive disorder characterized by defective intestinal electrolyte absorption, resulting in voluminous osmotic diarrhea with high chloride content. 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, altogether three founder and 17 private mutations have been characterized within miscellaneous ethnic groups. We screened for mutations in seven unrelated families with CLD. The diagnoses were confirmed by fecal chloride measurements. The combined PCR-SSCP and sequencing analyses revealed altogether seven novel mutations including two missense mutations (S206P, D468V), two splicing defects (IVS12-1G>C, IVS13-2delA), one nonsense mutation (Q436X), one insertion/deletion mutation (2104-2105delGGins29-bp), and an intragenic deletion of SLC26A3 exons 7 and 8. Two previously identified mutations were also found. This is the first report of rearrangement mutations in SLC26A3. Molecular features predisposing SLC26A3 for the two rearrangements may include repetitive elements and palindromic-like sequences. The increasingly wide diversity of SLC26A3 mutations suggests that mutations in the SLC26A3 gene may not be rare events.

Background: Neonatal septicemia (NNS) occurs frequently in neonatal intensive care units (NICU) and is often associated with high morbidity and mortality. However, information on its incidence and causative agents in Kuwait hospitals is scanty. Objectives: To investigate the bacterial causative agents of NNS in a NICU and their susceptibility patterns to antimicrobial agents. Methods: Between May 1 and December 31, 1996, blood cultures were performed on all admissions to the Neonatal Unit, Al-Jahra Hospital, Kuwait, with the Bactec 9240 instrument (Becton Dickinson, USA). Microorganisms were identified by cultural characteristics, Gram stain and biochemical profiles and antimicrobial susceptibility patterns performed by disk diffusion and by measuring their minimum inhibitory concentrations. Results: From a total of 995 neonates admitted to the neonatal unit during the study period, 117 (11.7%) had positive blood cultures. Eighty-seven (8.7%) of the neonates had confirmed septicemia. Gram-positive organisms were cultured from 65 (75%) and gram-negative organisms from 22 (25%) of them. The most frequent organisms isolated were Staphylococcus epidermidis (34%), Streptococcus viridans (28%) and Candida species (14%). Resistance to ampicillin and cephalosporins was detected in both gram-positive and gram-negative organisms associated with sepsis. Conclusions: The study identified the common bacterial pathogens associated with NNS in a neonatal unit, their susceptibility patterns to antimicrobial agents and emphasized the importance of understanding local epidemiology of NNS in formulating an antibiotic policy.

PurposeThe purpose was to report the structural, visual, and refractive outcomes of infants treated for retinopathy of prematurity (ROP) with laser and to identify the risk factors for unfavorable outcomes.Materials and methodsThe charts of infants with severe ROP treated by diode laser in a tertiary center during the period April 1999 to November 2003 were reviewed. Treated infants were followed up for fundus examination, visual acuity assessment, and cycloplegic refraction. Data regarding ocular risk factors, like zones of ROP and the extent of extraretinal proliferations, and data regarding various systemic risk factors were collected. A minimum follow up of 6 months was needed for inclusion in the study of structural outcome. A minimum follow up of 24 months was needed for the study of visual and refractive outcomes. The outcomes measured were: rate of unfavorable structural outcome, unfavorable visual outcome (visual acuity < 20/40), and high myopia (myopia ≥ 5 diopters). The ocular and systemic risk factors were studied for their significance in the development of unfavorable outcomes.ResultsTwo hundred seventy eyes of 148 infants were treated for severe ROP, out of which 20 eyes (7.4%) had unfavorable structural outcome. Visual data were available for 149 eyes of 81 infants, of which 70 eyes (47%) had unfavorable visual outcome. Refractive data were available for 131 eyes of 72 infants, and high myopia was present in 23 (17.6%) eyes. Zone I disease was the significant risk factor for unfavorable structural (P < 0.0001), unfavorable visual outcome (P = 0.03), and for high myopia (P < 0.0001). Lower post-conceptional age at treatment was significant for unfavorable structural outcome (P = 0.03) and high myopia (P < 0.0001). Presence of sepsis (P = 0.029) and extraretinal proliferation ≥ 6 hours were significant for unfavorable structural outcome (P = 0.002).ConclusionROP in zone I was the most significant risk factor for all the unfavorable outcomes. Laser-treated ROP infants need long term follow up.

We report on the first known Bedouin family with Greig cephalopolysyndactyly syndrome (MIM 175700). The index patient and his father shared pre- and postaxial polysyndactyly, mild mental retardation, and corpus callosum dysgenesis. Their phenotypic findings were compared with reported cases of both Greig cephalopolysyndactyly (GCPS) and acrocallosal syndromes. This family represents the second report of the rare occurrence of dysgenesis of the corpus callosum in GCPS.