Cross-colonisation seems to play an important role in the general spread of P. aeruginosa in ICUs.

The analysis of a de novo 8q12.2-q21.2 deletion led to the identification of a proposed previously undescribed contiguous gene syndrome consisting of Branchio-Oto-Renal (BOR) syndrome, Duane syndrome, hydrocephalus and trapeze aplasia. This is the first reported localization of the genes responsible for Duane syndrome and this dominant form of hydrocephalus. In contrast, we report a new localization for the gene responsible for BOR syndrome which is more telomeric to an initial placement. Linkage analysis of affected families consistently mapped the gene responsible for BOR and Branchio-Oto (BO) syndromes to within the deletion. Using new algorithms, a YAC contig was constructed and used to localize the breakpoint of another chromosomal rearrangement associated with BO syndrome to a 500 kb interval within the deletion. The 8q12.2-q21.2 deletion suggests that reduced dosage of the relevant genes is sufficient to cause Duane syndrome, BOR syndrome and this dominant form of hydrocephalus.

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To analyze the clinical features of hearing impairment and to search for correlations with the genotype in patients with DFNB1.Design: Case series.Setting: Collaborative study in referral centers, institutional practice.Patients: A total of 256 hearing-impaired patients selected on the basis of the presence of biallelic mutations in GJB2 or the association of 1 GJB2 mutation with the GJB6 deletion (GJB6-D13S1830)del. Main Outcome Measures:The prevalence of GJB2 mutations and the GJB6 deletion and audiometric phenotypes related to the most frequent genotypes.Results: Twenty-nine different GJB2 mutations were identified. Allelic frequency of 35delG was 69%, and the other common mutations, 313del14, E47X, Q57X, and L90P, accounted for 2.6% to 2.9% of the variants. Concerning GJB6, (GJB6-D13S1830)del accounted for 5% of all mutated alleles and was observed in 25 of 93 compound heterozygous patients. Three novel GJB2 mutations, 355del9, V95M, and 573delCA, were identified. Hearing impairment was frequently less severe in compound heterozygotes 35delG/L90P and 35delG/N206S than in 35delG homozygotes. Moderate or mild hearing impairment was more frequent in patients with 1 or 2 noninactivating mutations than in patients with 2 inactivating mutations. Of 93 patients, hearing loss was stable in 73, progressive in 21, and fluctuant in 2. Progressive hearing loss was more frequent in patients with 1 or 2 noninactivating mutations than in those with 2 inactivating mutations. In 49 families, hearing loss was compared between siblings with similar genotypes, and variability in terms of severity was found in 18 families (37%). Conclusion:Genotype may affect deafness severity, but environmental and other genetic factors may also modulate the severity and evolution of GJB2-GJB6 deafness.

Recent investigations identified a large deletion of the GJB6 gene in trans to a mutation of GJB2 in deaf patients. We looked for GJB2 mutations and GJB6 deletions in 255 French patients presenting with a phenotype compatible with DFNB1. 32% of the patients had biallelic GJB2 mutations and 6% were a heterozygous for a GJB2 mutation and a GJB6 deletion. Biallelic GJB2 mutations and combined GJB2/GJB6 anomalies were more frequent in profoundly deaf children. Based on these results, we are now assessing GJB6 deletion status in cases of prelingual hearing loss.