Spectrum and frequency of SLC26A4 mutations among Czech patients with early hearing loss with and without Enlarged Vestibular Aqueduct (EVA).

Mutations in SLC26A4 cause Pendred syndrome (PS) - hearing loss with goitre - or DFNB4 - non-syndromic hearing loss (NSHL) with inner ear abnormalities such as Enlarged Vestibular Aqueduct (EVA) or Mondini Dysplasia (MD). We tested 303 unrelated Czech patients with early hearing loss (298 with NSHL and 5 with PS), all GJB2-negative, for SLC26A4 mutations and evaluated their clinical and radiological phenotype. Among 115 available HRCT/MRI scans we detected three MD (2.6%), three Mondini-like affections (2.6%), 16 EVA (13 bilateral - 19.2% and 15.6% respectively) and 61 EVA/MD-negative scans (73.4%). We found mutation(s) in 26 patients (8.6%) and biallelic mutations in eight patients (2.7%) out of 303 tested. In 18 of 26 (69%) patients, no second mutation could be detected even using MLPA. The spectrum of SLC26A4 mutations in Czech patients is broad without any prevalent mutation. We detected 21 different mutations (four novel). The most frequent mutations were p.Val138Phe and p.Leu445Trp (18% and 8.9% of pathogenic alleles respectively). Among 13 patients with bilateral EVA, six patients (50%) carry biallelic mutations. In EVA -negative patients no biallelic mutations were found but 4.9% had monoallelic mutations. SLC26A4 mutations are present mostly in patients with EVA/MD and/or progressive HL and those with affected siblings.

Phenotypic variability of patients homozygous for the GJB2 mutation 35delG cannot be explained by the influence of one major modifier gene.

Hereditary hearing loss (HL) is a very heterogeneous trait, with 46 gene identifications for non-syndromic HL. Mutations in GJB2 cause up to half of all cases of severe-to-profound congenital autosomal recessive non-syndromic HL, with 35delG being the most frequent mutation in Caucasians. Although a genotype-phenotype correlation has been established for most GJB2 genotypes, the HL of 35delG homozygous patients is mild to profound. We hypothesise that this phenotypic variability is at least partly caused by the influence of modifier genes. By performing a whole-genome association (WGA) study on 35delG homozygotes, we sought to identify modifier genes. The association study was performed by comparing the genotypes of mild/moderate cases and profound cases. The first analysis included a pooling-based WGA study of a first set of 255 samples by using both the Illumina 550K and Affymetrix 500K chips. This analysis resulted in a ranking of all analysed single-nucleotide polymorphisms (SNPs) according to their P-values. The top 250 most significantly associated SNPs were genotyped individually in the same sample set. All 192 SNPs that still had significant P-values were genotyped in a second independent set of 297 samples for replication. The significant P-values were replicated in nine SNPs, with combined P-values between 3 x 10(-3) and 1 x 10(-4). This study suggests that the phenotypic variability in 35delG homozygous patients cannot be explained by the effect of one major modifier gene. Significantly associated SNPs may reflect a small modifying effect on the phenotype. Increasing the power of the study will be of greatest importance to confirm these results.

Corrosive injury of the oesophagus in children.

OBJECTIVE: This study examined a cohort of pediatric patients treated for suspected corrosive injury of the oesophagus in the ENT department between 1994 and 2003. METHODS: During the study period we examined 337 patients. All patients were treated according to an individual diagnostico-therapeutic protocol that included: foremost, early rigid oesophagoscopy; intensive medical therapy; nasogastric tube placement; and/or surgical intervention. RESULTS: Our proposed system of grading on a scale from 0 to 4 was used to classify the findings upon oesophagoscopy. One hundred eighty eight patients (55.7%) had a negative exam; 1st degree corrosive injury was present in 58 patients (17.4%); 2nd and 3rd degree injury in 81 patients (24%); and 4th degree was found in 10 patients (3%). CONCLUSIONS: Because the endoscopic findings were positive in 44% of patients with suspected corrosive injury, early rigid oesophagoscopy is indicated in all patients suspected of having corrosive injury even in the absence of clinical symptoms.

Corrosive oesophagitis in children following ingestion of sodium hydroxide granules--a case report.

Over the past few years, the ENT clinic in Motol has noticed an alarming increase in the number of cases of severe upper GIT injury in children, in the majority of cases caused by accidental ingestion of corrosives. Suicidal and homicidal cases in the paediatric population are rare. The following case study describes an interesting episode involving ingestion of granules of the lye NaOH in 13 children of school age. We furthermore stress the importance of early endoscopic investigation in every patient with possible corrosive injury of the oesophagus. We include a brief description of the diagnostico-therapeutic algorithm applied to each such patient that was developed through interdepartmental research in Motol Faculty Hospital.

Corrosive oesophagitis in children following ingestion of sodium hydroxide granules--a case report.

Over the past few years, the ENT clinic in Motol has noticed an alarming increase in the number of cases of severe upper GIT injury in children, in the majority of cases caused by accidental ingestion of corrosives. Suicidal and homicidal cases in the paediatric population are rare. The following case study describes an interesting episode involving ingestion of granules of the lye NaOH in 13 children of school age. We furthermore stress the importance of early endoscopic investigation in every patient with possible corrosive injury of the oesophagus. We include a brief description of the diagnostico-therapeutic algorithm applied to each such patient that was developed through interdepartmental research in Motol Faculty Hospital.